Iron deficiency reduces serum and in vitro secretion of interleukin-4 in mice independent of altered spleen cell proliferation

• Published in: Nutrition research (New York, N.Y.) Vol. 32; no. 2; pp. 107 - 115
• Main Authors: Kuvibidila, Solo R, Velez, Maria, Gardner, Renée, Penugonda, Kavitha, Chandra, Lawrance C, Yu, Lolie
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-02-2012; Elsevier
• Subjects: Anemia, Iron-Deficiency - blood; Anemia, Iron-Deficiency - immunology; Animals; Atrophy; Biological and medical sciences; CD3 Complex; CD4-Positive T-Lymphocytes - metabolism; Cell Proliferation; Concanavalin A; Cytokines; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology and Hepatology; Hematocrit; Hemoglobins - metabolism; Immunoglobulin E - blood; Interferon-gamma - metabolism; Interleukin-4; Interleukin-4 - blood; Interleukin-4 - secretion; Iron - administration & dosage; Iron - deficiency; Iron - immunology; Iron, Dietary - administration & dosage; Iron, Dietary - immunology; Iron, Dietary - therapeutic use; Liver - metabolism; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Organ Size; Spleen - cytology; Splenomegaly; Thymidine - metabolism; Thymus atrophy; Thymus Gland; Trace Elements - administration & dosage; Trace Elements - deficiency; Trace Elements - immunology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; iron deficient; interferon- γ; Interleukin-4; Thymus atrophy; C; Cytokines; concanavalin A; Con A; IL-13), interleukin-4 (interleukin-10, interleukin-13; iron-replete; Repl; control; Iron deficiency; IL-4 (IL-10; Anti-CD3; BSA; antibodies against the cluster of differentiation number 3; Fe def; FCS; fetal calf serum; Mice; bovine serum albumin; IFN- γ; IFN-γ; Cell proliferation; Spleen; Secretion; Iron deficiency anemia; Rodentia; Cytokine; Metabolic diseases; Hemopathy; Iron; Inorganic element; In vitro; Atrophy; Vertebrata; Interleukin 4; Mammalia; Mouse; Animal; Serum; Sideropenia
• ISSN: 0271-5317; 1879-0739
• DOI: 10.1016/j.nutres.2011.12.005

Abstract Iron deficiency, a worldwide public health problem in children and adult women, impairs innate and cell-mediated immunity including interferon- γ secretion. Its effects on interleukin (IL)-4 have not been well investigated. Interleukin-4, a cytokine primarily secreted by TH2 lymphocytes, regulates B-cell proliferation and the switching of immunoglobulin (Ig)M to IgE subtypes; the latter is involved in the defense against helminth infection. Considering the fact that interferon- γ is a potent inhibitor of IL-4, we hypothesize that iron deficiency would increase the secretion of IL-4 and IgE. We measured IL-4 in serum and supernatant of concanavalin A and anti-CD3 antibody-treated spleen cells from iron-deficient, control, pair-fed DBA and C57BL/6 mice (20-24/group) and iron-replete mice for 3, 7, and 14 days (8-13/group). Feeding the low-iron diet (5 ppm vs 50 ppm for the control diet) for 2 months significantly reduced the mean levels of hemoglobin, hematocrit, liver iron stores, thymus weight, and induced splenomegaly in both strains of mice ( P < .001). Iron deficiency, and not pair-feeding, reduced plasma IL-4 levels ( P < .05), although it did not significantly affect IgE levels. Iron deficiency, especially when associated with thymus atrophy, reduced in vitro IL-4 secretion by activated spleen cells, cell proliferation, and percentage of CD4+ IL-4+ cells ( P < .05). Impaired cell proliferation did not fully explain reduced in vitro IL-4 secretion because iron-deficient mice with a normal thymus weight had a normal3 H-thymidine uptake but decreased supernatant IL-4. It was likely due to low percentage of CD4+ IL-4+ . Iron repletion improved IL-4 measurements. Data suggest that iron deficiency has generalized negative effects on T-cell function. Unaltered plasma IgE may be due to other cytokines (ie, IL-13) that also modulate its secretion.