SYNERGY BETWEEN TUMOR-NECROSIS-FACTOR CT AND INTERLEUKIN-1 IN THE INDUCTION OF SICKNESS BEHAVIOR IN MICE

Like interleukin-1, recombinant human tumor necrosis factor alpha (TNF alpha) has been found to decrease social exploration and induce weigh t loss in mice in a dose and time-dependent manner. The present study was carried out to study the interaction between these two cytokines. Mice were injected IP with subthreshold doses of TNF alpha (2.5 mu g/m ouse) and IL-1 beta (50 ng/mouse). Social exploration was decreased 2 and 4 h after injection of TNF and IL-1, but body weight was not affec ted. Subthreshold doses of TNF alpha (90 ng/mouse) and IL-1 beta (100 pg/mouse) were also injected intracerebroventricularly (ICV). Social e xploration was decreased 1.5 and 3 h after injections of the two cytok ines and body weight was decreased for 6 h. To test the possibility of central induction of IL-1 by TNF alpha, mice pretreated with IL-1 rec eptor antagonist (IL-1ra, 1.8 mu g/mouse, ICV) were injected with 90 n g TNF alpha. Pretreatment with IL-1ra antagonized the depressive effec t of TNF alpha on behavior, but had no effect on weight loss induced b y this cytokine. These results suggest that TNF alpha-induced behavior al alterations are mediated by endogenously released IL-1, whereas met abolic changes are dependent on the release of other cytokines.