Anti-TNF-alpha antibody normalizes serum leptin in IL-2 deficient mice.
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-alpha (TNF-alpha), 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-alpha 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-alpha 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-alpha antibody increased significantly in the starved state. Serum concentrations of TNF-alpha were higher in IL-2(-/-) mice compared to controls in both the fed and starved state.


CONCLUSIONS
These results suggest that elevated TNF-alpha may be one mechanism for the sustained elevated leptin observed in IL-2(-/-) mice during food deprivation.
Gaetke
Lisa M
LM
Department of Nutrition and Food Science, University of Kentucky, and the Lexington Veterans Administration Medical Center, Lexington 40506-0054, USA. lgaetke@uky.edu
Oz
Helieh S
HS
Frederich
Robert C
RC
McClain
Craig J
CJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D001053:Apolipoproteins / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology; D004195:Disease Models, Animal; D005508:Food Deprivation; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D007376:Interleukin-2 / Q000097:blood / Q000172:deficiency*; D020738:Leptin / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000276:immunology* / Q000502:physiology*
D000911:Antibodies, Monoclonal; D001053:Apolipoproteins; D007376:Interleukin-2; D020738:Leptin; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha