Maternal milk, but not formula, regulates the immune response to beta-lactoglobulin in allergy-prone rat pups

J Nutr. 2009 Nov;139(11):2145-51. doi: 10.3945/jn.109.108845. Epub 2009 Sep 16.


Controversy exists regarding the timing of the introduction of allergic foods into the diet. We investigated the immune response of rat pups exposed to beta-lactoglobulin (BLG), one of the main allergenic proteins in cow milk. Brown Norway allergy-prone rats were allocated into groups: dam-reared and unchallenged (DR), DR challenged with BLG via gavage (11 mg/d), or rats fed via gastric cannula a formula containing BLG (11 mg/d). BLG was given from d 4 of life. Rats were killed at d 10, 14, or 21. Sera were assayed for total IgE, BLG-specific IgG1, and rat mucosal mast cell protease II (RMCPII; indicator of mucosal mast cell degranulation). Ileum was assessed for cytokine mRNA. Mesenteric lymph nodes (MLN) were assessed for forkhead boxP3 (Foxp3) and chemokine (C-C motif) receptor 7 (CCR7) expression by real-time PCR and immunostained for Foxp3(+) CD4(+) regulatory cells. Formula feeding compared with dam-rearing with or without oral BLG challenge resulted in significantly greater serum IgE, BLG-specific IgG1, RMCPII, and intestinal mast cells but reduced MLN Foxp3(+) cells, Foxp3, and CCR7 expression and ileal cytokines, interleukin (IL)-4, IL-10, and interferon-gamma (P < 0.05). Importantly, giving BLG in the presence of maternal milk resulted in an immune response profile similar to that of unchallenged DR rats but with greater Foxp3 and CCR7 mRNA expression and CD4(+) Foxp3(+) cells (P < 0.05). We conclude that introducing an allergenic food with breast milk reduces immunological indicators of an allergic response, whereas introduction during formula feeding generates an allergic response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / genetics
  • Female
  • Hypersensitivity / immunology*
  • Ileum / immunology
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Infant Formula / administration & dosage*
  • Lactoglobulins / immunology*
  • Mast Cells / immunology
  • Milk Hypersensitivity / immunology*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Inbred BN
  • Receptors, CCR7 / immunology
  • T-Lymphocytes, Regulatory / immunology


  • Ccr7 protein, rat
  • Cytokines
  • Immunoglobulin G
  • Lactoglobulins
  • RNA, Messenger
  • Receptors, CCR7
  • Immunoglobulin E