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.