Differential effects of iron deficiency and underfeeding on serum levels of interleukin-10, interleukin-12p40, and interferon-gamma in mice

BACKGROUND: Over-production of interferon-gamma (IFN-gamma) and under-production of interleukin-10 (IL-10) are associated with autoimmunity, whereas the opposite is associated with overwhelming infections. The influence of iron deficiency, a public health problem for children on in vivo secretion of these cytokines has not been previously investigated. OBJECTIVE: To determine whether iron deficiency alters serum levels of IFN-gamma, IL-10, and IL-12 in mice. DESIGN AND METHODS: Cytokine levels were measured by enzyme immunoassay in iron-deficient (ID), control (C), pair-fed (PF), and iron replete C57BL/6 mice for 3 (R3) and 14 (R14) days (n = 24-28, 12 R14). RESULTS: Iron deficiency was associated with > or = 50% reduction in hemoglobin, hematocrit, liver iron stores, and thymus weight (p < 0.05). Iron repletion improved these measurements. While iron deficiency significantly reduced IL-12p40 (64%) and IFN-gamma (66%) levels, underfeeding reduced those of IL-10 (48%) (p < 0.05). Iron repletion improved cytokine concentrations to PF levels. Thymus atrophy observed in 16 ID and 19 R3 mice, had no effect on IL-12p40 and IFN-gamma, whereas it further decreased IL-10 levels by 72% (p < 0.05). Cytokine levels positively correlated with indicators of iron status, body and thymus weights (r < or = 0.688, p < 0.05). CONCLUSION: Data suggest that iron deficiency alters the balance between pro- and anti-inflammatory cytokines, a change that may affect innate and cell-mediated immunity, and risk of autoimmune disorders.