The role of interleukin-6 in lipopolysaccharide-induced weight loss, hypoglycemia and fibrinogen production, in vivo.
It was recently shown that interleukin (IL)-6 is an important mediator involved in the Colon (C)-26 model of experimental cancer cachexia. In this study, we wished to determine whether IL-6 is also involved in several metabolic changes associated with lipopolysaccharide (LPS) challenge. Administration of a relatively high amount of LPS to mice induced a transient weight loss, hypoglycemia, hypertriglyceridemia and an increase in the hepatic acute phase reactant, fibrinogen. Pretreatment of mice with the rat anti-murine IL-6 antibody (20F3), but not with a control antibody, resulted in a significant improvement of LPS-induced hypoglycemia and weight loss as well as a significant decrease of plasma fibrinogen. Anti-IL-6 antibody had no effect on LPS-induced hypertriglyceridemia. On the other hand, the pretreatment of mice with anti-murine TNF (TN3.19) antibody was able to completely inhibit elevation of triglycerides and modestly improve LPS-induced weight loss although it had no effect on hypoglycemia and fibrinogen production. Taken together, these results suggest that IL-6 plays a role in some of the metabolic changes associated with both an acute (i.e. LPS challenge) and chronic (C-26 cachexia) inflammatory conditions.
Strassmann
G
G
Department of Immunology, Otuska America Pharmaceutical, Inc., Rockville, MD 20850.
Fong
M
M
Windsor
S
S
Neta
R
R
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002100:Cachexia / Q000503:physiopathology*; D004195:Disease Models, Animal; D004926:Escherichia coli; D005340:Fibrinogen / Q000378:metabolism*; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology; D015431:Weight Loss
D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D005340:Fibrinogen