Effects of iron deficiency on the secretion of interleukin-10 by mitogen-activated and non-activated murine spleen cells.
Interleukin (IL)-10 plays crucial regulatory roles in immune responses by inhibiting the secretion of several cytokines (IL-2, IL-12, interferon-gamma (IFN-gamma)) and lymphocyte proliferation. Iron deficiency, a public health problem for children, alters these immune responses. To determine whether these changes are related to altered IL-10 secretion, we measured IL-10 in 24 and 48 h supernatant of spleen cell cultures from iron deficient (ID), control (C), pairfed (PF), and ID mice fed the control diet (iron repletion) for 3 (R3) and 14 (R14) days (d, n = 12/group). Mean levels of hemoglobin, hematocrit, and liver iron stores varied as follows: C approximately equal PF approximately equal R14 > R3 > ID (P < 0.01). Mean baseline IL-10 levels of ID mice tended to be higher than those of other groups (P > 0.05, ANOVA). Mean IL-10 levels secreted by concanavalin A (Con A) and antibody raised against cluster of differentiation molecule 3 (anti-CD3)-treated cells (+/-background) were lower in ID than in C (48 h) and iron replete mice (P < 0.05). Underfeeding also reduced IL-10 secretion by anti-CD3-treated cells (48 h, P < 0.05). Lymphocyte proliferative responses to anti-CD3 +/- anti-CD28 antibodies were lower in ID than in C and PF mice, and they were corrected by iron repletion (P < 0.05). IL-10 levels negatively correlated with indicators of iron status (r <or= -0.285) and lymphocyte proliferation (r <or= -0.379 [r <or= -0.743 for ID mice]), but positively correlated with IFN-gamma levels (r <or= 0.47; P < 0.05). Data suggest that iron deficiency has a generalized deleterious effect on cells that secrete both cytokines. Reduced IL-10 secretion by activated cells does not overcome the inhibition of lymphocyte proliferation due to other factors of T cell activation that are regulated by iron.
D000818:Animals; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology*; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D007074:Immunoglobulin G / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism*; D000090463:Iron Deficiencies; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000378:metabolism*
D018106:CD28 Antigens; D017252:CD3 Complex; D006454:Hemoglobins; D007074:Immunoglobulin G; D008934:Mitogens; D003208:Concanavalin A; D016753:Interleukin-10