title: Iron deficiency reduces serum and in vitro secretion of interleukin-4 in mice independent of altered spleen cell proliferation.
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 normal (3)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.
authors.affiliation: Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA. solokuv@msn.com
authors.forename: Solo R
authors.initials: SR
authors.lastname: Kuvibidila
authors.forename: Maria
authors.initials: M
authors.lastname: Velez
authors.forename: Renée
authors.initials: R
authors.lastname: Gardner
authors.forename: Kavitha
authors.initials: K
authors.lastname: Penugonda
authors.forename: Lawrance C
authors.initials: LC
authors.lastname: Chandra
authors.forename: Lolie
authors.initials: L
authors.lastname: Yu
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000276:immunology*; D000818:Animals; D001284:Atrophy; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D049109:Cell Proliferation; D003208:Concanavalin A; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism*; D015847:Interleukin-4 / Q000097:blood / Q000378:metabolism*; D007501:Iron / Q000008:administration & dosage / Q000276:immunology; D000090463:Iron Deficiencies; D019266:Iron, Dietary / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009929:Organ Size; D013154:Spleen / Q000166:cytology*; D013163:Splenomegaly; D013936:Thymidine / Q000378:metabolism; D013950:Thymus Gland; D014131:Trace Elements / Q000008:administration & dosage / Q000172:deficiency / Q000276:immunology
chemical_list: D017252:CD3 Complex; D006454:Hemoglobins; D019266:Iron, Dietary; D014131:Trace Elements; D003208:Concanavalin A; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D007501:Iron; D013936:Thymidine