Interleukin-1 mediates behavioural but not metabolic effects of tumor necrosis factor alpha in mice.

Recombinant human tumor necrosis factor alpha (TNF alpha) decreases social exploration and induces weight loss in mice in a dose- and time-dependent manner (2.5-40 micrograms/mouse). To assess the role of interleukin-1 (IL-1) in these effects, mice pretreated with IL-1 receptor antagonist (IL-1ra, 500 micrograms/mouse, i.p.) were injected with 25 micrograms TNF alpha. Pretreatment with IL-1ra antagonized the depressive effects of TNF alpha on behaviour but only partially attenuated the weight loss induced by this cytokine. These results suggest that TNF alpha-induced sickness behaviour is mediated mainly by endogenously released IL-1 whereas metabolic changes are dependent on the release of other additional cytokines.