THE ROLE OF CYTOKINES IN THE BEHAVIORAL-RESPONSES TO ENDOTOXIN AND INFLUENZA-VIRUS INFECTION IN MICE - EFFECTS OF ACUTE AND CHRONIC ADMINISTRATION OF THE INTERLEUKIN-1-RECEPTOR ANTAGONIST (IL-1RA)

Following infection with influenza virus, animals display decreased lo comotor activity and feeding behavior and loss of body weight. It has been suggested that these effects may be mediated by cytokines, such a s interleukin-l (IL-1), interleukin-6 (1L-6) and tumor necrosis factor alpha (TNF-alpha), induced by the infection. To assess the potential role of IL-l, we tested the ability of a naturally occurring IL-l-rece ptor antagonist (IL-1ra) to antagonize the changes in feeding behavior induced by IL-1, endotoxin (lipopolysaccharide, LPS), and infection w ith influenza virus. Feeding behavior was assessed by measuring the da ily intake of food pellets and sweetened milk in a 30-min period. Acut e injection of IL-1 beta decreased milk intake, but mouse IL-6 and mou se TNF-alpha did not, However, TNF-alpha decreased food pellet intake slightly, especially when it was injected at the beginning of the dark phase. The reductions in mill; intake induced by mouse IL-1 beta were largely prevented by IL-1ra pretreatment (100 mu g/mouse i.p.). The L PS-induced reductions in milk intake were attenuated, but not blocked, by IL-1ra treatment (300 mu g/mouse). LPS still induced significant d ecrements in the presence of the antagonist. In influenza virus-infect ed mice, IL-1ra was administered either by repeated subcutaneous (s.c. ) injections, or by continuous s.c. infusion from osmotic minipumps. T hese IL-1ra treatments produced small, but statistically significant, attenuations of the depression in milk and food pellet intake in the v irus-infected mice. In several experiments, IL-1ra treatment increased the survival of influenza virus-infected mice. Thus the attenuation o f the hypophagia may have been caused by this IL-1ra-induced increase in survival. The results suggest that IL-1 contributes to sickness beh avior induced by LPS and influenza virus infection, but it is not the only factor involved. (C) 1997 Elsevier Science B.V.