Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/30/2006
Publication Date: 1/23/2007
Citation: Raqib, R., Hossain, M.B., Kelleher, S.L., Stephensen, C.B., Lonnerdal, B. Zinc Supplementation to Pregnant Rats with Adequate Zinc Nutriture Suppresses Immune Functions in their Offspring. Journal of Nutrition. 137: 1037-1042. Interpretive Summary: Zinc deficiency is common in many populations around the world due to low intake of animal foods and the presence of inhibitors of zinc absorption in many grain products. Zinc deficincy is associated with increased risk of common childhood infections, such as diarrhea, and this paper examined the impact of zinc deficiency in an animal model on the mucosal IgA response, and other aspects of infection. The IgA response protects against mucosal infections, such as diarrhea, and this work will help define how improving zinc nutriture can improve immune function and maintain health.
Technical Abstract: Background: Pronounced zinc (Zn) deficiency during pregnancy is associated with thymic and splenic atrophy and immunosuppression. However, our knowledge about consequences of marginal Zn deficiency and Zn supplementation during pregnancy on immune function in the offspring is limited. Aim: To study whether effects of mild Zn deficiency and subsequent supplementation with zinc during pregnancy persist after weaning and affect immune function of the offspring. Design: Adult rats were fed a Zn adequate diet (ZC, n=8) or a zinc deficient diet (ZD, n=8) preconception through lactation. Pregnant rats were supplemented with either (i) Zn (1.5 mg Zn/supplementation in water) or (ii) placebo (water) 3 times/wk throughout pregnancy. The pups were orally immunized with cholera toxin (CT) and bovine serum albumin-dinitrophenol (BSA-DNP) thrice at weekly intervals and killed 1 week after the last dose. Methods: Proliferation and cytokine response were studied in lymphocytes from Payer's patches and spleen; antigen specific antibodies were analyzed in plasma. Results: Zinc supplementation of Zn-deficient dams led to enhanced lymphocyte proliferation and interferon-gamma (IFN-g) responses in pups. In contrast, zinc supplementation of Zn-adequate dams led to suppression of these responses in the pups. Total and DNP-specific IgA responses were lower in pups of Zn-deficient group compared to the Zn-adequate group. Pups of Zn-deficient placebo supplemented dams had increased thymus size and body weight compared to the other groups at adulthood. Conclusion: Pre-pregnancy and early in utero Zn deficiency affected IgA responses in pups that could not be restored with maternal Zn supplementation during pregnancy. Zn supplementation to Zn-adequate dams induced immunosuppressive effects in utero that may also be mediated through milk and persists in the offspring after weaning.