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Akita EM, Li-Chan EC. Isolation of bovine immunoglobulin G subclasses from milk, colostrum, and whey using immobilized egg yolk antibodies. Journal of Dairy Science 81(1):54-63 (1998). Both IgG1 and IgG2 subclasses of IgG were isolated from bovine colostrum and milk. Removal of IgG1 and IgG2 also resulted in the removal of all IgG activity from the colostrum and milk.
PubMed Reference PMID:9493082
Armogida, SA, Yannaras, NM, Melton, AL, Srivastava, MD. Identification and quantification of innate immune system mediators in human breast milk. Allergy and Asthma Proceedings 25(5):297-304 (2004). Mediators of the innate immune system were determined in human colostrum. Human neutrophil-derived a-defensin 1 (HNP-1) and human beta-defensin 2 (HBD-2) were present in high amounts, human alpha-defensin 6 (HD-6) was present in moderate amounts, and HD-5 and HBD-1 were present in the lowest concentrations. HNP-1, HD-5 and HD-6 were present in significantly higher amounts in colostrum than in mature milk. It is believed that the innate immune system provides protection for both maternal breast tissue and the developing digestive system of newborns.
PubMed Reference PMID:15603202
Bishop GA, Haxhinasto SA, Stunz LL, Hostager BS. Antigen-specific B-lymphocyte activation. Critical Reviews in Immunology 23(3):159-197 (2003). B cells have the exclusive ability to produce and secrete immunoglobulins of various types. They also function in antigen presentation and the production of a number of cytokines and chemokines.
PubMed Reference PMID:14584878
Bitzan MM, Gold BD, Philpott DJ, Huesca M, Sherman PM, Karch H, Lissner R, Lingwood CA, Karmali MA. Inhibition of Helicobacter pylori and Helicobactor mustelae binding to lipid receptors by bovine colostrum. The Journal of Infectious Diseases 177(4):955-961 (1998). H. pylori causes gastric and duodenal ulcers in humans, and H. muselae is a gastric pathogen in ferrets. Both bind to phosphatidylethanolamine (PE), a phospholipid component of cell membranes in gastric mucosal cells. Bovine colostrum blocks attachment of the pathogens to PE. Colostral PE or PE derivatives also bind to the pathogens, inhibiting their ability to bind to target cells.
PubMed Reference PMID:9534968
Bocci V, Von Bremen K,
Corradeschi F, Luzzi E, Paulesu L. What is the role of
cytokines in human colostrum? Journal of Biological Regulators and
Homeostatic Agents. 5(4):121-124 (1991). Cytokines identified for the first time in colostrum, including interleukin (IL)-1, IL-6, interferon gamma, and tumor necrosis factor (TNF).
PubMed Reference PMID:1725087
Boesman-Finkelsein M, Walton NE, Finkelstein RA. Bovine lactogenic immunity against cholera toxin-related
enterotoxins and Vibrio cholerae outer membranes. Infection
and Immunity 57(4):1227-1234 (1989). Bovine colostrum provided immunity against cholera toxins and V. cholerae outer membranes. The immunoglobulin provided significant protection against diarrhea in baby rabbits which had been challenged intraintestinally with virulent cholera vibrios.
PubMed Reference PMID:2925248
Boesman-Finkelstein M. and Finkelstein R. Passive oral immunisation of children. Lancet 2(8675):1336 (1989). Passive immunization children against rotavirus (main cause of diarrhea in young children) using immunoglobin from bovine colostrum.
PubMed Reference PMID2574282
Bogstedt AK, Johansen K, Hatta H, Kim M, Casswall T, Svensson L, Hammarstrom L. Passive immunity against diarrhoea. Acta Paediatrica 85(2):125-128 (1996). Effectiveness of passive oral immunization using bovine immunoglobulin from colostrum.
PubMed Reference PMID:8640033
Bottcher MF, Jenmalm MC, Bjorksten B. Cytokine, chemokine and secretory IgA levels in human milk in relation to atopic disease and IgA production in infants. Pediatric Allergy and Immunology 14(1):35-41 (2003). Human breast milk contains IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-16, interferon gamma, transforming growth factors beta 1 and beta 2, and other cytokines. None of their levels correlated with the appearance of atopic (allergic) symptoms during the first two years of life.
PubMed Reference PMID:12603709
Brinkmann V, Geiger T, Alkan S, Heusser CH. Interferon alpha increases the frequency of interferon gamma-producing human CD4+ T cells. Journal of Experimental Medicine 178(5):1655-1663 (1993). Allergic disease and chronic infections are marked by an increased ration of T helper cells type 2 (Th2), resulting in immune dysregulation. Th2 cells produce increased levels of IL-4 and decreased levels of interferon gamma. Interferon alpha was shown to favor the induction and maintenance of Th1 cells, counteracting Th2-driven allergic responses.
PubMed Reference PMID:8228812
Brock JH, Ortega F, Pineiro A. Bactericidal and hemolytic activity of complement in bovine colostrum and serum: effect of proteolytic enzymes and ethylene glycol tetraacetic acid (EGTA). Annales d’Immunologie 126C(4):439-451 (1975). Bovine colostrum has bactericidal activity against an enteropathic strain of E. coli. Low but significant levels of complement in colostrum appear to be responsible for this activity, and the activity appears to be modulated by classical complement pathway rather than the alternate pathway which appears to operate in bovine serum.
PubMed Reference PMID:813560
Bryan DL, Hawkes JS, Gibson RA. Interleukin-12 in human milk. Pediatric Research 45(6):858-859 (1999). IL-12 was found in human colostrum and milk. The concentration dropped with time.
PubMed Reference PMID:10367778
Buescher ES, McWilliams-Koeppen P. Soluble tumor necrosis factor-alpha (TNF-alpha) receptors in human colostrum and milk bind to TNF-alpha and neutralize TNF-alpha bioactivity. Pediatric Research 44(1):37-42 (1998). Tumor necrosis factor-alpha (TNF-alpha) receptors in human colostrum and milk can bind to TNF-alpha and block its bioactivity. This is most likely a way of modulating TNF-alpha activity in the colostrum and milk.
PubMed Reference PMID:9667368
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Casswall TH, Sarker SA, Albert MJ, Fuchs GJ, Bergstrom M, Bjorck L, Hammarstrom L. Treatment of Helicobacter pylori infection in infants in rural
Bangladesh with oral immunoglobulins from hyperimmune bovine colostrum. Alimentary Pharmacology and Therapeutics 12(6):563-568 (1998). Bangladeshi children infected with H. pylori (a principal cause of ulcers and gastrointestinal disease in children) were given immunoglobulins from hyperimmune bovine colostrum. None became negative for H. pylori, probably because infection is very common in high endemic areas, so reinfection prevents proper evaluation of the effectiveness of the treatment.
PubMed Reference PMID:9678817
Cesarone MR, Belcaro G, Di Renzo A, Dugall M, Cacchio M, Ruffini I, Pellegrini L, Del Boccio G, Fano F, Ledda A, Bottari A, Ricci A, Stuard S, Vinciguerra G. Prevention of influenza episodes with colostrum compared with vaccination in healthy and high-risk cardiovascular subjects: the epidemiologic study in San Valentino. Clinical and Applied Thrombosis/Hemostasis 13(2):13-16 (2007). Two month supplementation with oral colostrum was compared to anti-influenza vaccination in the prevention of flu. Colostrum was at least three times more effective than vaccination in preventing flu.
PubMed Reference PMID:17456621
Chan MC, Cheung CY, Chui WH, Tsao SW, Nicholls JM, Chan YO, Chan RW, Long HT, Poon LL, Guan Y, Peiris JS. Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respiratory Research 6:135 (2006). H5N1 influenza A viruses are much more potent inducers of pro-inflammatory cytokines, including IP-10, RANTES, interferon-beta, and IL-6 in human alvelolar and bronchial epithelial cells. This hyper-induction of inflammatory cytokines is the most dangerous and lethal action of H5N1.
PubMed Reference PMID:16283933
Collins AM, Roberton DM, Hosking CS, Flannery GR. Bovine milk, including pasteurised milk, contains antibodies directed against allergens of clinical importance to man. International Archives of Allergy and Applied Immunology 96(4):362-367 (1991). Pasteurised and raw bovine milk and bovine colostrum samples were assayed by enzyme-linked immunoassay for the presence of antibodies directed against a selection of allergens of importance in human atopic disease. Samples were tested for the presence of antibodies directed against or cross-reacting with ryegrass pollen, house dust mites, Aspergillus mould and wheat proteins. Antibodies of each specificity were detected in every sample tested.
PubMed Reference PMID:1809694
Davidson GP, Whyte PB, Daniels E, Franklin K, Nunan H, McCloud PI, Moore AG, Moore DJ. (1989)
Passive immunisation of children with bovine colostrum containing
antibodies to human rotavirus. Lancet 2(8665):709-12. Children given colostral immunoglobulin against rotavirus were protected from infection during a hospital visit, while those in the control group had a high incidence of infection.
PubMed Reference PMID:2570959
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Ebina T, Sato A, Umezu K, Ishida N, Ohyama S, Ohizumi A, Aikawa K, Katagiri S, Katsushima N, Imai A. Prevention of rotavirus infection by cow colostrum containing antibody
against human rotavirus. Lancet. 2(8357):1029-1030 (1983). Immunoglobulin from cows hyperimmunized against rotavirus showed good protective effects on infants exposed to rotavirus. 6 of 7 infants who received milk only came down with rotavirus-induced diarrhea, while only 1 of 6 who received the immunoglobulin did.
PubMed Reference PMID:4069083
Eggena MP, Barugahare B, Jones N, Okello M, Mutalya S, Kityo C, Mugyenyi P, Cao H. Depletion of regulatory T cells in HIV infection is associated with immune activation. Journal of Immunology 174(7):4407-4414 (2005). Immune activation during chronic HIV infection is a strong clinical predictor of death and may mediate helper CD4+ T cell depletion. Regulatory T cells actively down-regulate immune responses. In a study using 81 Ugandan volunteers, it was found that depletion of regulatory T cells occurs at different rates than other CD4+ T cells, resulting in an increased regulator to helper ratio in many patients with advanced disease. This skewing may contribute to T cell effector dysfunction.
PubMed Reference PMID:15778406
Feldmann M, Brennan F, Maini R. Role of
cytokines in rheumatoid arthritis. Annual Review of Immunology 14:397-440 (1996). This study confirmed that TNF-α is the major controlling factor in the inflammatory response seen in rheumatoid arthritis. Therefore the ability of colostrum to modulate the activity of TNF-α may be the way in which colostrum is of benefit to those suffering from rheumatoid arthritis (and other types of arthritis as well).
PubMed Reference PMID:8717520
Feldmann M, Maini RN. The role of cytokines in the pathogenesis of rheumatoid arthritis. Rheumatology 38(suppl 2):3-7 (1999). The down-regulation of TNF-alpha, the cytokine that controls the inflammatory cascade of cytokines, has proven a useful therapeutic target in the treatment of rheumatoid arthritis.
PubMed Reference PMID:10646481
Garofalo R, Chheda S, Mei F, Palkowetz KH, Rudloff HE, Schmalstieg FC, Rassin DK, Goldman AS. Interleukin-10 in human milk. Pediatric Research 37(4pt1):444-449 (1995). IL-10 was found to be present in human colostrum milk up to 80 hours postpartum.
PubMed Reference PMID:7596683
Gerson C, Sabater J, Scuri M, Torbati A, Coffey R, Abraham JW, Lauredo I, Forteza R, Wanner A, Salathe M, Abraham WM, Conner GE. The lactoperoxidase system functions in bacterial clearance of airways. American Journal of Respiratory Cell and Molecular Biology 22(6):665-671 (2000). Lactoperoxidase, a component of airway mucus, is one of the principal defenses against respiratory infection. Thiocyanate is present in the mucus in sufficient concentration for the lactoperoxidase system to be effective. Airway lactoperoxidase forms the biocidal compound hypothiocyanate. It is largely responsible for bacterial clearance of the airways.
PubMed Reference PMID:10837362
Hagiwara K, Kataoka S, Yamanaka H, Kirisawa R, Iwai H. Detection of cytokines in bovine colostrum. Veterinary Immunology and Immunopathology 76(3-4):183-190 (2000). ELISA specific for bovine cytokines detected five cytokines in bovine colostrum: IL-1β, IL-6, INF-α, INF-γ, and IL-1 ra (receptor antagonist).
PubMed Reference PMID:11044552
Hagiwara K, Yamanaka H, Higuchi H, Nagahata H, Kirisawa R, Iwai H. Oral administration of IL-1 beta enhanced the proliferation of lymphocytes and the O(2)(-) production of neutrophils in newborn calf. Veterinary Immunology and Immunopathology 81(1-2):59-69 (2001). Calves given labeled IL-1 beta orally showed that it was passively transferred to the calves. The calves also showed a significant increase in white blood cell count. IL-1 beta has an immunostimulatory effect.
PubMed Reference PMID:11498247
Hanson LA, Ahlstedt S, Andersson B, Carlsson B, Cole MF, Cruz JR, Dahlgren U, Ericsson TH, Jalil F, Khan SR, Mellander L, Schneerson R, Eden CS, Soderstrom T, Wadsworth C. Mucosal Immunity. Annals of the New York Academy of Sciences
409:1-21 (1983). Many factors come into play in providing defense against pathogens on the mucosal membranes of the body. These include secretory immunoglobulin A (sIgA), immunoglobulin G (IgG), and oligosaccharides (which prevent attachment of pathogens to mucosal lining cells) all play a role. All are found in colostrum.
PubMed Reference PMID:6191608
Hashira S, Okitsu-Negishi S, Yoshino K. Interleukin 8 in the human colostrum. Biology of the Neonate 82(1):34-38 (2002). Human colostrum contains IL-8.
PubMed Reference PMID:12119539
Hazenburg MP, Klasen IS, Kool J, Ruseler-van Embden JG, Severijnen AJ. Are intestinal bacteria involved in the etiology of rheumatoid arthritis? AMPIS, 100(1):1-9 (1992). The fact that there is a connection between bowel-related joint inflammation and bacteria give support to this hypothesis. Tests with cell wall fragments from intestinal bacteria were found to produce joint inflammation in animal models. Given that the human intestinal tract contains large amounts of these bacteria, it is reasonable to deduce that bacterial cell wall fragments may play a role in human arthritis of unknown etiology.
PubMed Reference PMID:1536716
Hilpert H, Brussow H, Mietens C, Sidoti J,
Lerner L, Werchau H. Use of bovine milk concentrate containing
antibody to rotavirus to treat rotavirus gastroenteritis in infants. Journal
of Infectious Diseases 156(1):158-166 . Infants hospitalized with rotavirus gastroenteritis that were given IgG from hyperimmunized cows showed a significant reduction in the duration of excretion of the virus compared to controls.
PubMed Reference PMID:3110303
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Huppertz H, Rutkowski S, Busch D, Eisebit R,
Lissner R, Karch H. (1999) Bovine colostrum ameliorates diarrhea in
infection with diarrheagenic Escherichia coli, shiga toxin producing
E. coli, and E-coli expressing intimin and hemolysin. Journal of
Pediatric Gastroenterology and Nutrition. 29(4):452-456 (1987). Pooled colostrum was given to infants infected with diarrheagenic E. coli, shiga toxin producing E. coli, or enterohemorrhagic E.coli expressing intimin and hemolysin experienced diminished frequency of loose stools compared to placebo. The colostrum was well tolerated.
PubMed Reference PMID:10512407
Jochims K, Kaup FJ, Drommer W, Pickel M. An immunoelectron microscopic investigation of colostral IgG
absorption across the intestine of newborn calves. Research in
Veterinary Science 57(1):75-80 (1994). Colostral IgG is transported across the intestinal boundary in newborn calves by specialized vesicles, called coated vesicles.
PubMed Reference PMID:7973097
Keller MA, Heiner DC, Myers AS, Reisinger DM. IgD in human colostrum. Pediatric Research 19(1):122-126 (1985). Concentrations of IgD in human colostrum were measured in a range from 2.2-410 µg/dl (mean concentration 35 µg/dl).
PubMed Reference PMID:3969303
Kelleher SL. Lonnerdal B. Immunological activities associated with milk. Advances in Nutritional Research 10:39-65 (2001). Milk and colostrum not only provide the necessary nutritional requirements of the newborn but also establish the normal gut flora that inhibit the growth of pathogens and transfer maternal immunity to the infant.
PubMed Reference PMID:11795053
Kelly CP, Pothoulakis C, Vavva F, Castagliuolo I, Bostwick EF, O'Keane JC, Keates S, LaMont JT. Anti-Clostridium difficile bovine immunoglobulin concentrate inhibits cytotoxicity and enterotixicity of C. difficile toxins. Antimicrobial Agents and Chemotherapy 40(2):373-379 (1996). Immunoglobulin from hyperimmunized cows neutralizes the toxins from C. difficile, thus making it useful in prevention and treatment of C.difficile diarrhea.
PubMed Reference PMID:8834883
Khazenson L, Gennad'eva T, Roshchin V,
Krasheniuk A, Semenova N. Activity of bovine colostral IgG in
the human digestive tract. Zhurnal Mikrobiologii, Epidemiologii, i Immunobiologii
9:101-106 (1980). The biological activity of bovine IgG from colostrum from cows hyperimmunized against Shigella sonnei was measured as it passed through the intestinal tracts of adults. Although the concentration of intact IgG decreased as it passed through the tract, anti-Shigella activity remained high, indicating that the digestion of the intact IgG produced biologically active fragments.
PubMed Reference PMID:7004026
Kohl S, Malloy, M, Pickering L, Morriss F,
Adcock E, Walters D. Human colostral cytotoxicity: I.
Antibody-dependent cellular cytotoxicity against herpes simplex
viral-infected cells mediated by colostral cells. Journal of
Clinical Laboratory Immunology. 1(3):221-224 (1978). Cells from colostrum in combination with antibody were able to kell Herpes simplex virus-infected cells. Cells without the antibody had very low cytotoxicity.
PubMed Reference PMID:756470
Korhonen H, Suvaoja EL, Ahola-Luttilia H, Sivela S, Kopola S, Husu J, Kosunen TU. Bactericidal effect of bovine normal and immune serum,
colostrum and milk against Helicobactor pylori. Journal of Applied
Bacteriology 78(6):655-662 (1995). Both serum and colostrum but not milk from cows was found to be highly bactericidal against H. pylori.
PubMed Reference PMID:7615421
Korhonen H, Marnila P, Gill HS. Milk immunoglobulins and complement factors. British Journal of Nutrition 84(Suppl 1):S75-S80 (2000). In bovine colostrum IgG1 accounts of 75% of the total Ig, followed by IgM, IgA and IgG2.
PubMed Reference PMID:11242450
Kussendrager KD, van Hooijdonk AC. Lactoperoxidase: physico-chemical properties, occurrence, mechanism of action and applications. British Journal of Nutrition 84(Suppl 1):S19-S25 (2000). Lactoperoxidase catalyzes the inactivation of a wide range of microorganisms by means of the lactoperoxidase system.
PubMed Reference PMID:11242442
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Lawton JW, Shortridge KF, Wong RL, Ng MH. Interferon synthesis by human colostral leucocytes. Archives of Diseases of Children 54(2):127-130 (1979). Colostral leucocytes (white blood cells) stimulated to produce interferon did so, but were less efficient than blood leucocytes.
PubMed Reference PMID:434888
LeFranc-Millot C, Vercaigne-Marko D, Wal J.-M,
Lepretre A, Peltre G, Dhulster P, Guillochon D. Comparison of the IgE titers to bovine colostral G
immunoglobulins and the F(ab')2 fragments in sera of
patients allergic to milk. International Archives of Allergy and Immunology
110(2):156-162 (1996). IgE titers against colostral IgG were significantly higher in 36% of those suffering from milk allergy, while the digested fragments of IgG showed significantly less immunoreactivity while maintaining immunoreactivity.
PubMed Reference PMID:8645993
Lehrer RI, Lichtenstein AK Ganz, T. Defensins: antimicrobial and cytotoxic peptides of mammalian cells. Annual Reviews of Immunology 11:105-128 (1993). Defensins, small peptides containing 29-35 amino acids, are antimicrobial and cytotoxic components of the innate immune system. They are known to be antimicrobial against both gram positive and gram negative bacteria, mycobacteria (tuberculosis and leprosy), Treponema pallidum (the spirochete that causes syphilis), many fungi, and some enveloped viruses. They are also cytotoxic against a wide range of normal and malignant cells, including cells resistant to TNF-alpha and NK-cytolytic factor. They act by attaching to the cell membranes of target microorganisms and cells, penetrating them and making them permeable, which leads to lysis. Some defensins function as opsonins, some inhibit protein kinase C, some bind specifically to the ACTH receptor and block steroidogenesis, and some act as specific chemoattractants for monocytes.
Pubmed Reference PMID:8476558
Lissner R, Thurmann P, Merz G, Karch, H. Antibody reactivity and fecal recovery of bovine immunoglobulins
following oral administration of a colostrum concentrate from cows to
healthy volunteers. International Journal of Clinical Pharmacology
and Therapeutics 36(5):239-245 (1998). Pooled colostrum exhibited reactivity against proteins from Yersinia enterocolitica and Campylobacter jejuni, both powerful pathogens which cause gastrointestinal diseases.
PubMed Reference PMID:9629986
Loimaranta V, Carlen A, Olsson J, Tenovuo J,
Syvaoja E.-L, Korhonen H. Concentrated bovine colostral whey
proteins from Streptococcus mutans/Strep. sobrinus immunized cows
inhibit the adherence of Strep. mutans and promote the aggregation of
mutans streptococci. Journal of Dairy Research 65(4):599-607 (1998). Colostral whey proteins from cows immunized against Streptococcus mutans and Streptococcus sobrinus were tested to determine their effect on adherence and aggregation of these two bacteria which cause dental cavities. The whey from cows immunized against the bacteria significantly inhibited adherence and increased aggregation compared to whey from non-immunized cows.
PubMed Reference PMID:9839215
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Mach JP, Pahud JJ, Isliker H. IgA with “secretory piece” in bovine colostrum and saliva. Nature 223(209):952-955 (1969). Secretory IgA found in bovine colostrum.
PubMed Reference PMID:4184794
Michalek SM, McGhee JR. Effective
immunity to dental caries: passive transfer to rats to antibodies to
Streptococcus mutans elicits protection. Infection and Immunity
17(3):644-650 (1977). IgG derived from colostrum, milk and blood serum of rats immunized against Streptococcus mutans (which cause dental cavities) effectively immunized the offspring of these rats against the bacteria. Fewer cavities were found in the offspring than in non-immunized rats.
PubMed Reference PMID:903178
Mickelson KN, Moriarty KM. Immunoglobulin levels in human colostrum and milk. Journal of Pediatric Gastroenterology and Nutrition 1(3):381-4 (1982). Levels of sIgA, IgG and IgM were determined in human colostrum and milk. A mean concentration of 32 g/L was found for sIgA (1.5-83.7 g/L), 1.13 g/L for IgM and 0.53 g/L for IgG. While total amounts declined with time postpartum, relative proportions remained the same.
PubMed Reference PMID:7186050
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Milgrom H. Attainments in atopy: special aspects of allergy and IgE. Advances in Pediatrics 49:273-297 (2002). Allergy is characterized by elevated levels of specific IgE in the blood, called “atopy”. Therapy with anti-IgE has shown promise in inhibiting early- and late-phase allergic reactions and asthma. [Colostrum contains both IgE and IgE-blockers.]
PubMed Reference PMID:12214775
Mitra AK, Mahalanabis D, Ashraf H, Unicomb L,
Eeckels R, Tzipori S. Hyperimmune cow colostrum reduces
diarrhoea due to rotavirus: a double-blind, controlled clinical trial. Acta Paediatrica 84(9):996-1001 (1995). Colostrum from cows immunized against four strains of rotavirus (the leading cause of diarrhea in infants) was given to infants aged 6-24 months who were infected with the virus. Those receiving the colostrum experienced a 29% reduction in the duration of the diarrhea compared to the control group, and diarrhea stopped in 50% of them whereas all of the control group continued to experience diarrhea.
PubMed Reference PMID:8652974
Mohan P, Haque K. Oral immunoglobulin for the prevention of rotavirus infection in low birth weight infants. Cochrane Database System Review 3:CD003740 (2003). Rotavirus is the most common neonatal virus infection, causing severe diarrhea, and is potentially lethal to low birth weight infants. Boosting mucosal immunity with orally administered immunoglobulin from colostrum can help prevent infection. No adverse effects have been reported in trials.
PubMed Reference PMID:12917985
Nord J, Ma P, DiJohn D, Tzipori S, Tacket CO. Treatment with bovine hyperimmune colostrum of cryptosporidial diarrhea in AIDS patients. AIDS. 4(6):581-584 (1990). Cryptosporidium parvum can cause severe, debilitating diarrhea in AIDS patients. In this pilot study, treatment with hyperimmune colostrum against C. parvum showed promise in treating patients with cryptosporidosis.
PubMed Reference PMID:2201320
Ogra P, Losonsky G, Fishaut M. Colostrum-derived immunity and maternal-neonatal interaction. Annals of the New
York Academy of Sciences 409:82-95 (1983). Colostrum from the mother is important in establishing the immune system in newborn humans.
PubMed Reference PMID:6347005
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Ogra SS, Ogra PL. Immunologic aspects of
human colostrum and milk. I. Distribution characteristics and concentrations of immunoglobulins at different times after the onset of lactation. Journal of Pediatrics.
92(4):546-549 (1978). While levels of IgG remain fairly constant following the onset of lactation, levels if IgA and IgM decline rapidly in humans.
PubMed Reference PMID:416193
Ouwehand A, Salminen S, Skurnik M, Conway P. Inhibition of pathogen adhesion by B-lactoglobulin. International Dairy Journal. 7:685-692 (1997). Beta-lactoglobulin, a component of colostrum, inhibited the adhesion of Klebsiella oxytoca and a strain of fimbriae-expressing E. coli to immobilized iliostomy glycoproteins (a model of intestinal mucosa). Inhibition of adhesion may prevent colonization of pathogens at an early stage of infection.
Palmer EL, Gary Jr. GW, Black R, Martin ML. Antiviral activity of colostrum and serum immunoglobulins A and
G. Journal of Medical Virology. 5(2):123-129 (1980). Human colostrum contains IgA specific to enteric virus but no virus-specific IgG.
PubMed Reference PMID:6246196
Parodi PW. Cows' milk fat components as potential anticarcinogenic agents. Journal of Nutrition 127(6):1055-1060 (1997). Conjugated linoleic acid, a component of cow's milk and colostrum, inhibits proliferation of human malignant melanoma, colorectal, breast and lung cancer cell lines. It also has been shown to reduce the incidence of chemically induced mouse epidermal tumors, mouse forestomach neoplasia, and aberrant crypt foci in rats. It also inhibits mammary tumorogensis. Sphingomyelin, one of the phospholipids in colostrum and milk, participates in three major antiproliferative pathways - inhibition of cell growth, induction of differentiation, and apoptosis (programmed cell death) - through its biologically active metabolites ceramide and sphingosine. Milk triaglycerides also contain butyric acid, a potent inhibitor of proliferation and inducer of differentiation and apoptosis in a wide range of neoplastic cell lines. Other anti-cancer components of colostrum and milk include beta-carotene, beta-ionone and gossypol.
PubMed Reference PMID:9187617
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Paulik S, Slanina L, Polacek M. [Lysozyme in the colostrum and blood of calves and dairy cows] Veterinarni Medicina 30(1):21-28 (1985). In first colostrum the lysozyme concentration fluctuated within the range of 0.15 to 0.65 µg/ml, with an average of 0.30 µg/ml. The concentration of lysozyme and immunoglobulins of the IgG and IgM class in colostrum showed a contrary trend in first and second milk yield, with a tendency towards increase for lysozyme and towards decrease for immunoglobulins.
PubMed Reference PMID:3918380
Petschow B, Talbott R. Reduction in
virus-neutralizing activity of a bovine colostrum immunoglobulin
concentrate by gastic acid and digestive enzymes. Journal of
Pediatric Gastroenterology and Nutrition . 19(2):228-235 (1994). Gastric acid and pancreatic trypsin (a digestive enzyme) reduce the biological activity of bovine milk antibodies as they pass through the digestive tract.
PubMed Reference PMID:7815246
Petzoldt K, von Benten C. Passive allergisation of calves and lambs due to colostral antibodies. Annales de recherches vétérinaires 9(2):235-238 (1978). This study demonstrates that newborn calves are passively sensitized by oral intake of maternal anaphylactic antibodies.
PubMed Reference PMID:747320
Pincus C, Nussenweig V. Regulation of the
Immune Response: Suppressive and enhancing effects of passively
administered antibody. Journal of Experimental Medicine.
133(5):987-1003 (1971). The immune response can be modulated through the passive administration of antibody, such as the IgG in colostrum.
PubMed Reference PMID:4101806
Plettenberg A, Stoehr.A, Stellbrink J, Albrecht H, Meigel W. A preparation from bovine colostrum in the treatment of HIV-positive patients with chronic diarrhea. Clinical Investigator 71(1):42-45 (1993). Treatment with 10 grams of IgG from bovine colostrum per day led to either partial or complete remission of symptoms in 64% of tested patients with chronic refactory diarrhea due to HIV infection.
PubMed Reference PMID:8453259
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Quigley JD, Martin KR, Dowlen HH, Wallis LB,
Lamar K. Immunoglobulin concentration, specific gravity, and
nitrogen fractions of colostrum from Jersey cattle. Journal of
Dairy Science 77(1):264-269 (1994). Colostrum collected from cows as soon after parturition as possible and analyzed for levels of immunoglobulin, fat and nitrogen. IgG content decreased and IgA content increased with time in the colostrum.
PubMed Reference PMID:8120194
Radosevich JK, Scott GH, Olson GB. Delayed-type hypersensitivity responses induced by bovine colostral components. American Journal of Veterinary Research, 46(4):875-878 (1985). Transfer factor-type substances obtained from leukocytic cells and fluid portions of bovine colostrum caused effective passive transfer of delayed-type hypersensitivity responses across species barriers. Passive transfer of Brucella abortus sensitivity was obtained when using components derived from colostrum of dams sensitized at 3 and 9 months of age. Colostral feedings to calves caused the passive transfer of delayed-type hypersensitivity as early as 2 days after parturition. The findings indicated that colostral components were important in the process of cell-mediated immunity.
PubMed Reference PMID:3925823
Rudloff HE, Schmalstieg FC Jr, Mushtaha AA, Palkowetz KH, Liu SK, Goldman AS. Tumor necrosis factor-alpha in human milk. Pediatric Research 31(1):29-33 (1992). Tumor necrosis factor-alpha is found in human colostrum and milk in sufficient quantities to affect the immune system of the infant.
PubMed Reference PMID:1375729
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Walker M. Bovine colostrum offers
broad-spectrum benefits for wide-ranging ailments. Townsend Letters for
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gastroenteritis. Acta Paediatrica 87(3):264-267 (1998). Hyperimmune bovine colostrum showed some improvement in the duration and severity of rotaviral diarrhea in otherwise healthy, well-fed children, but the results were not statistically significant.
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Yoshioka, Y, Kudo, S, Nishimura, H, Yajima, T, Kishihara, K, Saito, K, Suzuki, T, Suzuki, Y, Kuroiwa, S, Yoshikai, Y. Oral administration of bovine colostrum stimulates intestinal intraepithelial lymphocytes to polarize Th1-type in mice. International Immunopharmacology 5(3):581-590 (2005). Stimulating the Th1 immune response from the Th2 skewed immune response in infancy is important to reduce the incidence of allergies. Mice given colostrum showed a polarization to Th1 response in intestinal intraepithelial lymphocytes while intestinal microflora and IgA levels showed no change. This suggests that colostrum may protect from both infectious disease and allergies mediated by Th2 type responses.
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Antibiotic Abuse
Costanzo SD, Murby J, Bates J. Ecosystem response to antibiotics entering the aquatic environment. Marine Pollution Bulletin 51(1-4):218-223 (2005). Antibiotics in effluent from treatment plants could be detected up to a half kilometer from the point of entry. Bacteria in the water near the effluent discharge points tended to be antibiotic resistant.
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Dagan R, Barkai G, Leibovitz E, Dreifuss E, Greenberg D. Will reduction of antibiotic use reduce antibiotic resistance?: The pneumococcus paradigm. Pediatric Infectious Disease Journal 25(10):981-986 (2006). Antibiotic abuse is the leading cause of antibiotic-resistant strains of pathogenic bacteria. However, not all antibiotics produce resistant strains equally. In the case of Streptococcus pneumococcus, the cause of pneumonia in young children, amoxicillin is the least resistance-promoting, while cephalosporins and azithromycin have a higher resistance-promoting potential. However, all antibiotics promote resistance to some degree.
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Lewis R. The Rise of Antibiotic-Resistant Infections. US Food and Drug Administration http://www.fda.gov/fdac/features/795_antibio.html
Loganathan B, Phillips M, Mowery H, Jones-Lepp TL. Contamination profiles and mass loadings of macrolide antibiotics and illicit drugs from a small urban wastewater treatment plant. Chemosphere 75(1):70-77 (2009). A study of wastewater treatment effluents showed that a number of antibiotics and illegal drugs (methamphetamine and ecstasy) remain in the water after processing and thus enter the environment. The efficiency of removal varied between different antibiotics varied from virtually all with urobilin to only 47% with azithromycin. Only 54.5% of methamphetamine was removed.
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Nusslein K, Arnt L, Rennie J, Owens C, Tew GN. Broad-spectrum antibacterial activity by a novel abiogenic peptide mimic. Microbiology 152 (Pt. 7):1913-1918 (2006). As resistant strains of pathogens increase and antibiotic efficacy wanes, researchers have been searching for replacement therapies. One promising solution is a class of peptides known as antimicrobial peptides (AMP) which are found in both vertebrates and invertebrates as a part of the innate defense system. Modern technology has made it possible to design similar peptides with high specificity and therefore much less probability of creating resistance.
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Pallasch TJ. Antibiotic prophylaxis: problems in paradise. Dental Clinics of North America 47(7):665-679 (2003). The age of antibiotic prophylaxis may be receding into its twilight years because the assumption upon which it was based has not proved generally true. Although antibiotics treat infections, limited benefit has been demonstrated in preventing infections. These are two entirely different biologic entities, a distinction which appears to have gone unappreciated by many for more than 50 years. If the principles of antibiotic prophylaxis established more than 40 years ago had been assiduously followed, many of its abuses could have been avoided. This may not have stopped our legal colleagues, but it would have been worth an effort on behalf of our patients. It is likely that the massive overuse of antibiotics as litigation prevention has contributed to the global epidemic of antibiotic-resistant micro-organisms and an unknown number of serious adverse effects to the antibiotics themselves. Even with this abuse, much money has still flowed from defendant to plaintiff. Substantial data exist that antibiotics do not prevent bacteremias. The absolute risk rate for bacterial endocarditis after dental treatment even in at-risk patients is very low. Antibiotic prophylaxis for surgical infections requires specific dosing schedules (perioperative surgical prophylaxis) to be successful.
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Pallasch TJ. Antibiotic resistance. Dental Clinics of North America 47(4):623-639 (2003). Through billions of years of evolution, microbes have developed myriad defense mechanisms designed to ensure their survival. This protection is readily transferred to their fellow life forms via transposable elements. Despite very early warnings, humans have chosen to abuse the gift of antibiotics and have created a situation where all microorganisms are resistant to some antibiotics and some microorganisms are resistant to all antibiotics. When antibiotics are used, six events may occur with only one being beneficial: when the antibiotic aids the host defenses to gain control and eliminate the infection. Alternatively, the antibiotic may cause toxicity or allergy, initiate a superinfection with resistant bacteria, promote microbial chromosomal mutations to resistance, encourage resistance gene transfer to susceptible species, or promote the expression of dormant resistance genes.
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Salleh A. Antibiotics Flushed into Waterways. ABC News (Australia) March 17, 2005. http://www.abc.net.au/science/articles/2005/03/17/1324969.htm
Sancho-Puchades M, Herraez-Vilas JM, Berini-Aytes L, Gay-Escoda C. Antibiotic prophylaxis to prevent local infection in Oral Surgery: use or abuse? Medicina Oral, Patología Oral y Cirugía Bucal 14(1)E28-E33 (2009). The use of antibiotics to prevent local infections in fit patients questionable. Many clinical trials have questioned the effectiveness of antibiotics in preventing wound infection. More effective are anti-infectious measures that minimize infection risk during the healing period of the wound.
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Arteaga A, Santa-Olalla P, Sierra MJ, Limia A, Cortes M, Amela C. [Epidemic risk of disease associated with a new strain of Clostridium difficile.] Enfermedades Infecciosas y Microbiologia Clinica Epub ahead of print (2009). Clostridium difficile (C. dificile) infections have increased in North America and Europe over the last few decades, mostly as a result of antibiotic abuse. A new strain of C. difficile, known as toxigenic type III, has increased pathogenicity and antibiotic resistance resulting in the threat of an epidemic if immediate steps are not taken. [Article in Spanish]
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Borody TJ, Surace R, Warren E. Tunnel vision in the bowel. Center for Digestive Diseases (2001). Review of irritable bowel syndrome, including ulcerative colitis and Crohn's disease, and its etiology, including infective agents such as Shigella and Campylobacter. Infections of the gut are difficult to treat because no antimicrobial therapy is available that is effective against Clostridia spores. Only bovine colostrum has proven clinical efficacy in eradicating intestinal pathogens, such as rotavirus, and may help control the infections seen in chronic disorders such as irritable bowel syndrome due to the number of biologically active components in colostrum. The growth factors in colostrum help heal intestinal erosions and ulcerations. It also contains anti-inflammatory factors and is nutrient rich. Colostrum may be used alone or in combination with other anti-inflammatory and/or immune substances. Future research should focus on identifying immune strategies, novel delivery systems and identification of the bioactives in colostrum.
Carver JD, Barness LA. Trophic factors for the gastrointestinal tract. Clinical Perinatology 23(2):265-285 (1996). Factors in colostrum which promote the development of the GI tract in newborn infants also help protect against such diseases as Crohn’s disease, colitis, necrotizing enterocolitis and diarrhea.
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of Internal Medicine Supplement 732:145-154 (1990). The intestinal mucosa has multiple layers of protection to prevent the absorption of unwanted and/or dangerous materials. These include the unstirred water/mucous layers, apical and basolateral cell membranes of the epithelial cell, the intercellular junctions, the intestinal matrix, and the capillary and lymphatic endothelia. It is able to restrict the movement of solutes as small as 3Å while allowing permeation by some larger molecules such as albumin, which has a 36Å radius. Permeability is significantly altered in certain physiologic and pathologic conditions.
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malabsorption. American Journal of Medicine. 67(6):1077-1084 (1979).Intestinal immune responses occur at external mucosal surfaces. Much of the immunity stems from Peyer's patches - large collections of lymphocytes in the intestine which take in antigens, sensitize lymphocytes to them, and then release the lymphocytes into the intestinal lumen.
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Galland, L. Leaky Gut Syndromes: Breaking the Vicious Cycles. Townsend Letter for Doctors 145:62 (1995, Aug/Sept). Toxins ofmany kinds can increase intestinal permeability. These include alcohol, nonsteroidal anti-inflammatory drugs (aspirin, ibuprofen, arthritis medications, and many others), cytotoxic drugs used to treat cancer, corticosteroid drugs, and, by their action on bowel flora, antibiotics.
Gastrointestinal Inflammation and Repair Group, Imperial College, London (2003). Unpublished research. In an in vitro experimental study, colostrum stimulated intestinal cell growth and reestablished a healthy epithelial layer following injury. In an in vivo experimental study, colostrum powder was also shown to reduce gastric injury.
Gionchetti, P, Rizzello, F, Campieri, M. Probiotics in gastroenterology. Current Opinion in Gastroenterology 18(2):235-239 (2002). Probiotics are of benefit in the prevention of gastrointestinal diseases, such as viral diarrhea, Clostridium difficile-associated diarrhea, traveler's diarrhea (shigellosis), antibiotic-associated diarrhea, H. pylori infection, irritable bowel syndrome, radiotherapy-associated diarrhea, and inflammatory bowel disease.
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Graul T, Cain AM, Karpa KD. Lactobacillus and bifidobacteria combinations: A strategy to reduce hospital-acquired Clostridium difficile diarrhea incidence and mortality. Medical Hypotheses 73(2):194-198 (2009) (e-pub). Clostridium dificile- associated disease (CDAD) is increasing, particularly in hospital and other health-related settings. Routine use of probiotics in such settings could be used to protect patients from CDAD by normalizing disrupted gastrointestinal flora.
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Kim JW, Jeon WK, Yun JW, Park DI, Cho YK, Sung IK, Sohn CI, Kim BI, Yeom JS, Park HS, Kim EJ, Shin MS. Protective effects of bovine colostrum on non-steroidal anti-inflammatory drug induced intestinal damage in rats. Asia Pacific Journal of Clinical Nutrition 14(1):103-107 (2005). NSAIDs given to animals have much the same effect as they do in humans, namely, increased intestinal permeability, increased enteric bacteria levels, villous loss, and loss of enteric protein and albumin. Supplementation with bovine colostrum reduced the increase in intestinal permeability, the enteric bacteria overgrowth, the lose of proteins, and villous damage.
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(1999). Non-steroidal Anti-inflammatory Drugs are effective against arthritis but cause gastrointestinal injury. Taking colostrum prior to NSAIDs reduced gastric injury by up to 60%.
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Playford RJ, MacDonald CE, Johnson WS. Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders. American Journal of Clinical Nutrition 72(1):5-14 (2000). Colostrum or peptides derived from it are useful for the treatment of a wide variety of gastrointestinal conditions, including inflammatory bowel disease, NSAID-induced gut injury, and chemotherapy-induced mucositis.
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Prosser C, Stelwagen K, Cummins R, Guerin P, Gill N, Milne C. Reduction in heat induced gastrointestinal hyperpermeability in rats by bovine colostrum and goat milk powders. Journal of Applied Physiology 96:650-654 (2004). Bovine colostrum healed “leaky gut” in an experimental rat model using heat induced gastrointestinal hyperpermeability.
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PubMed Reference PMID:3318588
Warny M, Fatimi A, Bostwick EF, Laine DC, Lebel F, LaMont JT, Pothoulakis C, Kelly CP. Bovine immunoglobulin concentrate-clostridium difficile retains C difficile toxin neutralising activity after passage through the human stomach and small intestine. Gut 44(2):212-217 (1999). A bovine colostrum IgG concentrate specific against C. difficile resists digestion in the GI tract and retains its toxin-A binding abiliity and neutralizing activity is retained.
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