Anti-Inflammatory Characteristics of Human Milk

How, Where, Why
  • E. Stephen Buescher
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 501)


When first proposed, the hypothesis that human milk was anti-inflammatory was supported by 2 observations: poor function of milk leukocytes and the presence in milk of components that could modify inflammatory processes. This hypothesis is now supported by studies documenting anti-inflammatory effects in animal models and suppression of humoral and cellular components of inflammation in vitro. To date, two mechanisms have been demonstrated: alteration of leukocyte function and modification of cytokine biology. It is not clear whether these mechanisms are only topical effects in the digestive tract, or whether absorption of milk components results in systemic effects. While inflammation benefits the host as a defense mechanism and precursor to immune responses, it also contributes to the clinical manifestations of illness and is an important early component of wound-healing responses that result in scar. The biological effects of milk’s anti-inflammatory character may be to minimize clinical symptomatology without losing immunoresponsiveness for the breast-fed infant, and to minimize scar formation during healing responses.


Human Milk Reactive Oxygen Metabolite Microbicidal Activity Milk Component Reprod Immunol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arend WP, Malyak M, Smith MF Jr, Whisenand TD, Slack JL, Sims JE, Giri JG, Dower SK. Binding of IL-1 alpha, IL-1 beta and IL-1 receptor antagonist by soluble IL-1 receptors and levels of soluble IL-1 receptors in synovial fluids. J Immunol 1994;153:4766–4774.PubMedGoogle Scholar
  2. Bauchner M, Leventhal JM, Shapiro ED. Studies of breast-feeding and infection: how good is the evidence? JAMA 1986;256:887–892.CrossRefPubMedGoogle Scholar
  3. Beaudry M, Dufour R, Marcoux S. Relation between infant feeding and infections during the first 6 months of life. J Pediatr 1995;126:191–197.CrossRefPubMedGoogle Scholar
  4. Bhaskaram P, Reddy V. Bactericidal activity of human milk leukocytes. Acta Paediatr Scand 1981;70:87–90.CrossRefPubMedGoogle Scholar
  5. Biondi A, Peri G, Colombo N, Bolis G, Mantovani A. Antibody-dependent and -independent cytotoxicity of human mononuclear phagocytes: defective stimulation of tumoricidal activity in milk macrophages. Clin Exp Immunol 1982;49:701–708.PubMedGoogle Scholar
  6. Bjorksten B, Gothefors L, Sidenvall R. The effect of human colostrum on neutrophil function. Pediatr Res 1979;13:737–741.CrossRefPubMedGoogle Scholar
  7. Blackwell TS, Blackwell TR, Holden EP, Christman BW, Christman JW. In vivo antioxidant treatment suppresses nuclear factor-kappa B activation and neutrophilic lung inflammation. J Immunol 1996; 157:1630–1637.PubMedGoogle Scholar
  8. Bocci V, von Bremen K, Corradeschi F, Franchi F, Luzzi E, Paulesu L. Presence of interferon-y and interleukin-6 in colostrum of normal women. Lymphokine Cytokine Res 1993;12:21–24.PubMedGoogle Scholar
  9. Buescher ES, Malinowska I. Soluble receptors and cytokine antagonists in human milk. Pediatr Res 1996; 40:839–844.CrossRefPubMedGoogle Scholar
  10. Buescher ES, Koeppen PM. Soluble TNFa receptors in colostrum bind to and neutralize TNF z. Pediatr Res 1997;41:80A.CrossRefGoogle Scholar
  11. Buescher ES, Mcllheran SM. Antioxidant properties of human milk. Pediatr Res 1988;24:14–19.CrossRefPubMedGoogle Scholar
  12. Buescher ES, Mcllheran SM. Colostral antioxidants: separation and characterization of two activities in human colostrum. J Pediatr Gastroenterol Nutr 1992;47–56.Google Scholar
  13. Buescher ES, Mcllheran SM. Polymorphonuclear leukocytes and human colostrum: effects of in vivo and in vitro exposure. J Pediatr Gastroenterol Nutr 1993;17:424–433.CrossRefPubMedGoogle Scholar
  14. Crockett-Torabi E, Ward PA. The role of leukocytes in tissue injury. Eur J Anaesthesiol 1996;13:235–246.CrossRefPubMedGoogle Scholar
  15. Cummings NP, Neifert MR, Pabst MJ, Johnston RB Jr. Oxidative metabolic responses and microbicidal activity of human milk macrophages: effect of lipopolysaccharide and muramyl dipeptide. Infect Immun 1985;49:435–439.PubMedGoogle Scholar
  16. Diegelmann RF. Cellular and biochemical aspects of normal and abnormal wound healing: an overview. J Urol 1997;157:298–302.CrossRefPubMedGoogle Scholar
  17. Eglinton BA, Roberton DM, Cummins AG. Phenotype of T cells, their soluble receptor levels, and cytokine profile of human breast milk. Immunol Cell Biol 1994;72:306–313.CrossRefPubMedGoogle Scholar
  18. France GL, Marmer DJ, Steele RW. Breast feeding and salmonella infection. Am J Dis Child 1980; 134:147–152.PubMedGoogle Scholar
  19. Garofalo R, Chheda S, Mei F, Palkowetz KH, Rudloff HE, Schmalsteig FC, Rassin DK, Goldman AS. Interleukin-10 in human milk. Pediatr Res 1995;37:444–449.CrossRefPubMedGoogle Scholar
  20. Gianella RA. Importance of the intestinal inflammatory reaction in salmonella-mediated intestinal secretion. Infect Immun 1979;23:140–145.Google Scholar
  21. Gilmore WS, McKelvey-Martin VJ, Rutherford S, Strain JJ, Loane P, Kell M, Millar S. Human milk contains granulocyte colony stimulating factor. Eur J Clin Nutr 1994;48:222–224.PubMedGoogle Scholar
  22. Goldman AS. The immune system of human milk: antimicrobial, anti-inflammatory and immunomodulating properties. Pediatr Infect Dis J. 1993;12:664–671.CrossRefPubMedGoogle Scholar
  23. Goldman AS, Thorpe LW, Goldblum RM, Hanson LA. Anti-inflammatory properties of human milk. Acta Paediatr Scand 1986;75:689–695.CrossRefPubMedGoogle Scholar
  24. Goldman AS, Goldblum RM, Hanson LA. Anti-inflammatory systems in human milk. Adv Exp Med Biol 1990;262:69–76.CrossRefPubMedGoogle Scholar
  25. Gordon LI, Douglas SD, Kay NE, Yamada O, Osserman EF, Jacob HS. Modulation of neutrophil function by lysozyme. J Clin Invest 1979;64:226–232.CrossRefPubMedGoogle Scholar
  26. Grazioso CF, Buescher ES. Inhibition of neutrophil function by human milk. Cell Immunol 1996; 168:125–132.CrossRefPubMedGoogle Scholar
  27. Grazioso CF, Werner AL, Ailing DW, Bishop PR, Buescher ES. Anti-inflammatory effects of human milk on chemically-induced colitis in rats. Pediatr Res 1997;42:639–643.CrossRefPubMedGoogle Scholar
  28. Grulee EG, Sanford HN, Schwarz H. Breast and artificially fed infants. J Am Med Assoc 1934;103:735–739.CrossRefGoogle Scholar
  29. Hanson LA, Carlsson B, Jalil F, Hahn-Zoric M, Hermodson S, Karlberg J, Mellander L, Khan SR, Lindblad B, Thiringer K, Zaman S. Antiviral and antibacterial factors in human milk. In: Hanson LA, editor. Biology of Human Milk. Volume 15, Nestlé Nutrition Workshop Series. New York: Raven Press; 1988. pp 141–157.Google Scholar
  30. Ho PC, Lawton JWM. Human colostral cells: phagocytosis and killing of E. coli and C. albicans. J Pediatr 1978;93:910–915.CrossRefGoogle Scholar
  31. Ho FCS, Wong RLC, Lawton JWM. Human colostral and breast milk cells. Acta Paediatr Scand 1979; 68:389–396.CrossRefPubMedGoogle Scholar
  32. Iacono VJ, MacKay BJ, DiRienzo S, Pollock JJ. Selective antibacterial properties of lysozyme for oral micro-organisms. Infect Immun 1980;29:623–632.PubMedGoogle Scholar
  33. Jansson L, Akesson B, Holmberg L. Vitamin E and fatty acid composition of human milk. Am J Clin Nutr 1981;34:8–13.PubMedGoogle Scholar
  34. Johnson DF, France GL, Marmer DL, Steele RW. Bactericidal mechanisms of human breast milk leukocytes. Infect Immun 1980;28:314–318.PubMedGoogle Scholar
  35. Keeney SE, Schmalsteig FC, Palkowetz KH, Rudloff E, Binh-Minh L, Goldman AS. Activated neutrophils and neutrophil activators in human milk: increased expression of CD1 lb and decreased expression of L-selectin. J Leukoc Biol 1993;54:97–104.PubMedGoogle Scholar
  36. Khan AJ, Rosenfeld W, Vadapalli M, Biagton J, Khan P, Huq A, Evans HE. Chemotaxis and random migration of human milk cells. J Pediatr 1980;96:879–882.CrossRefPubMedGoogle Scholar
  37. Mandalapu P, Pabst HF, Paetkau V. A novel immunosuppressive factor in human colostrum. Cell Immunol 1995;162:178–184.CrossRefPubMedGoogle Scholar
  38. Mandyla H, Xanthou M, Maravelias C, Baum D, Matsaniotis N. Antibody dependent cytotoxicity of human colostrum phagocytes. Pediatr Res 1982;16:995–999.CrossRefPubMedGoogle Scholar
  39. Martinez GA, Dodd DA, Samartgedes JA. Milk feeding patterns in the United States during the first 12 months of life. Pediatrics 1981;68:863–868.PubMedGoogle Scholar
  40. Morrow AL, Reyes RR, West MS, Guerrero ML, Ruiz-Palacios GM, Pickering LK. Protection against infection with Giardia lamblia by breast-feeding in a cohort of Mexican infants. J Pediatr 1992;121:363–370.CrossRefPubMedGoogle Scholar
  41. Mullberg J, Schooltink H, Gunther M, Graeve L, Mackiewicz A, Heinrich PC, Rose-John S. The soluble interleukin-6 receptor is generated by shedding. Eur J Immunol 1993;23:473–480.CrossRefPubMedGoogle Scholar
  42. Munoz C, Endres S, van der Meer J, Schlesinger L, Arevalo M, Dinarello C. Interleukin- 1 ß in human colostrum. Res Immunol 1990;141:505–513.CrossRefPubMedGoogle Scholar
  43. Murphey DK, Buescher ES. Human colostrum has anti-inflammatory activity in a rat subcutaneous air pouch model of inflammation. Peditar Res 1993;34:208–212.CrossRefGoogle Scholar
  44. Newburg DS, Viscidi RP, Ruff A, Yolken RH. A human milk factor inhibits binding of human immunodeficiency virus to the CD4 receptor. Pediatr Res 1992;31:22–28.CrossRefPubMedGoogle Scholar
  45. Noda K, Umeda M, Ono T. Transforming growth factor activity in human colostrum. Gann 1984;75:109–112.PubMedGoogle Scholar
  46. Oksenberg JR, Persitz E, Brautbar C. Cellular immunity in human milk. Am J Reprod Immunol 1985; 8:125–129.Google Scholar
  47. Ostrea EA, Balun JE, Winkler R, Porter T. Influence of breast-feeding on the restoration of the low serum concentration of vitamin E and ß-carotene in the newborn infant. Am J Obstet Gynecol 1986; 154:1014–1017.Google Scholar
  48. Ozkaragoz F, Rudloff HB, Rajaraman S, Mushtaha AA, Schmalsteig FC, Goldman AS. The motility of human milk macrophages in collagen gels. Pediatr Res 1988;23:449–452.PubMedGoogle Scholar
  49. Palkowetz KH, Royer CL, Garofalo R, Rudloff HE, Schmalsteig FC, Goldman AS. Production of interleukin-6 and interleukin-8 by human mammary gland epithelial cells. J Reprod Immunol 1994;26:57–64.CrossRefPubMedGoogle Scholar
  50. Park SS, Samiy N, Ruoff K, D’Amico DJ, Baker AS. Effect of intravitreal dexamethasone in treatment of pneumococcal endophthalmitis in rabbits. Arch Ophthalmol 1995;113:1324–1329.CrossRefPubMedGoogle Scholar
  51. Perdomo OJ, Cavaillon JM, Huerre M, Ohayon H, Gounon P, Sansonnetti PJ. Acute inflammation causes epithelial invasion and mucosal destruction in experimental shigellosis. J Exp Med 1994;180:1307–1319.CrossRefPubMedGoogle Scholar
  52. Pickering LK, Cleary TG, Kohl S, Getz S. Polymorphonuclear leukocytes of human colostrum. I. Oxidative metabolism and kinetics of killing of radiolabeled Staphylococcus aureus. J Infect Dis 1980; 142:685–693.CrossRefPubMedGoogle Scholar
  53. Popkin BM, Adair L, Akin JS, Black R, Briscoe J, Flieger W. Breast-feeding and diarrheal morbidity. Pediatrics 1990;86:874–882.PubMedGoogle Scholar
  54. Prentice A, Ewing G, Roberts SB, Lucas A, MacCarthy A, Jarjou LMA, Whitehead RG. The nutritional role of breast milk IgA and lactoferrin. Acta Paediatr Scand 1987;76:592–598.CrossRefPubMedGoogle Scholar
  55. Pryor BD, Bologna SG, Kahl LE. Risk factors for serious infection during treatment with cyclophosphamide and high-dose corticosteroids for systemic lupus erythematosus. Arthritis Rheum 1996;39:1475–1482.CrossRefPubMedGoogle Scholar
  56. Ravichandran KS, Collins TL, Burakoff SJ. CD4 and signal transduction. In: Littman DR, editor. The CD4 Molecule, Roles in T Lymphocytes and in HIV Disease. Curr Top Microbiol Immunol 1994;205:47–62.Google Scholar
  57. Robinson JE, Harvey BAM, Soothill JE. Phagocytosis and killing of bacteria and yeast by human milk cells after opsonization in aqueous phase of milk. BMJ 1978;1:1443–1445.CrossRefPubMedGoogle Scholar
  58. Rodriguez C, Subiza RC, Mateos P, Casado de Frias E, Moro M, De la Concha EG. Comparative functional study of colostral macrophages from mothers delivering preterm and at term. Acta Paediatr Scand 1989;78:337–341.CrossRefPubMedGoogle Scholar
  59. Rudloff HE, Schmalsteig FC, Mushtaha AA, Palkowetz KH, Liu SK, Goldman AS. Tumor necrosis factor-alpha in human milk. Pediatr Res 1992;31:29–33.CrossRefPubMedGoogle Scholar
  60. Rudloff HE, Schmalsteig FC, Palkowetz KH, Paskiewicz EJ, Goldman AS. Interleukin-6 in human milk. J Reprod Immunol 1993;23:13–20.CrossRefPubMedGoogle Scholar
  61. Ruiz-Palacios GM, Calva JJ, Pickering LK, Lopez-Vidal Y, Volkow P, Pezzarossi H, West MS. Protection of breast-fed infants against Campylobacter diarrhea by antibodies in human milk. J Pediatr 1990;116:707–713.CrossRefPubMedGoogle Scholar
  62. Saito S, Maruyama M, Kato Y, Moriyama I, Ichijo M. Detection of IL-6 in human milk and its involvement in IgA production. J Reprod Immunol 1991;20:267–276.CrossRefPubMedGoogle Scholar
  63. Saito S, Yoshida M, Ichijo M, Ishizaka S, Tsujii T. Transforming growth factor-beta (TGF-(3) in human milk. Clin Exp Immunol 1993;94:220–224.CrossRefPubMedGoogle Scholar
  64. Sanchez L, Calvo M, Brock JH. Biological role of lactoferrin. Arch Dis Child 1992;67:657–661.CrossRefPubMedGoogle Scholar
  65. Sone S, Tsutsumi H, Takeuchi R, Matsuda K, Imai S, Ogra PL, Chiba S. Enhanced cytokine production by milk macrophages following infection with respiratory syncytial virus. J Leukoc Biol 1997;61:630–636.PubMedGoogle Scholar
  66. Speer CP, Gahr M, Pabst MJ. Phagocytosis-associated oxidative metanolism in human milk macrophages. Acta Paediatr Scand 1986;75:444–451.CrossRefPubMedGoogle Scholar
  67. Srivastava MD, Srivastava A, Brouhard B, Saneto R, Groh-Wargo S, Kubit J. Cytokines in human milk. Res Commun Mol Pathol Pharmacol 1996;93:263–287.PubMedGoogle Scholar
  68. Stevenson SS. The adequacy of artificial feeding in infancy. J Pediatr 1947;31:616–630.CrossRefPubMedGoogle Scholar
  69. Strober W, Kelsall B, Fuss I, Marth T, Ludviksson B, Ehrhardt R, Neurath M. Reciprocal IFN-gamma and TGF-beta responses regulate the occurrence of mucosal inflammation. Immunol Today 1997;18:61–64.CrossRefPubMedGoogle Scholar
  70. Thorpe LW, Rudloff HE, Powell LC, Goldman AS. Decreased response of human milk leukocytes to chemoattractant peptides. Pediatr Res 1986;20:373–377.CrossRefPubMedGoogle Scholar
  71. Tsuda H, Takeshige K, Shibata Y, Minakami S. Oxygen metabolism of human colostral macrophages: comparison with monocytes and polymorphonuclear leukocytes. J Biochem 1984;95:1237–1245.PubMedGoogle Scholar
  72. Victora CG, Fuchs SC, Flores JAC, Fonseca W, Kirkwood B. Risk factors for pneumonia among children in a Brazilian metropolitan area. Pediatrics 1994;93:977–985.PubMedGoogle Scholar
  73. Wahl SM. Inflammation and growth factors. J Urol 1997;157:303–305.CrossRefPubMedGoogle Scholar
  74. Wallace JM, Ferguson SJ, Loane P, Kell M, Millar S, Gillmore WS. Cytokines in human breast milk. Br J Biomed Sci 1997;54:85–87.PubMedGoogle Scholar
  75. Walley KR, Lukacs NW, Standiford TJ, Streiter RM, Kunkel SL. Balance of inflammatory cytokines related to severity and mortality of murine sepsis. Infect Immun 1996;64:4733–4738.PubMedGoogle Scholar
  76. Welsh JK, May JT. Anti-infective properties of breast milk. J Pediatr 1979;94:1–9.CrossRefPubMedGoogle Scholar
  77. Whitby DJ, Ferguson MWJ. Immunohistochemical localization of growth factors in fetal wound healing. Dev Biol 1991;147:207–215.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • E. Stephen Buescher
    • 1
  1. 1.Center for Pediatric ResearchEastern Virginia Medical SchoolNorfolk

Personalised recommendations