Anti-TNF-α Antibody Normalizes Serum Leptin in IL-2 Deficient Mice

Abstract

Objective: A recent study reports that the interleukin-2 deficient (IL-2−/−) mouse model of autoimmune and inflammatory bowel disease (IBD) with elevated pro-inflammatory cytokine production has elevated leptin concentrations during food deprivation. The objective of this study was to examine whether increased tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, contributes to the abnormally elevated leptin in IL-2−/− mice.Methods: Eight week old, IL-2−/− and wild-type control (IL-2+/+), male mice were fed regular laboratory mouse food for two weeks. At the end of the study, blood was collected in the fed state, IL-2−/− and IL-2+/+ mice were injected with either anti-TNF-α monoclonal antibody or normal saline, and blood was collected in the starved state.Results: The IL-2−/− mice consumed less food and lost weight. Administration of anti-TNF-α antibody markedly reduced serum leptin concentrations in IL-2−/− and control mice after food deprivation. Serum leptin in the IL-2−/− mice not receiving anti-TNF-α antibody increased significantly in the starved state. Serum concentrations of TNF-α were higher in IL-2−/− mice compared to controls in both the fed and starved state.Conclusions: These results suggest that elevated TNF-α may be one mechanism for the sustained elevated leptin observed in IL-2−/− mice during food deprivation.