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-γ)) 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 ≈ PF ≈ R14 > R3 > ID (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 ≤ −0.285) and lymphocyte proliferation (r ≤ −0.379 [r ≤ −0.743 for ID mice]), but positively correlated with IFN-γ levels (r ≤ 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. J. Cell. Biochem. 90: 278–286, 2003. © 2003 Wiley-Liss, Inc.