SYNERGISTIC EFFECT OF RHTNF-ALPHA AND RHIL-1-ALPHA IN INDUCING ANOREXIA IN RATS

To investigate whether there is a synergistic effect of recombinant hu man tumor necrosis factor-alpha (rhTNF-alpha) and recombinant human in terleukin-1 alpha (rhIL-1 alpha) in inducing anorexia, 32 rats with ju gular catheters were studied (8 rats/group): controls received normal saline; the IL-1 group received rhIL-1 alpha (10 mu g/kg); the TNF gro up received rhTNF-alpha (30 mu g/kg); and the IL-1 + TNF group receive d the same concentration of both rhIL-1 alpha + rhTNF-alpha for 3 days ; solutions were then switched to normal saline. No significant decrea se in light- and dark-phase food intake occurred during infusion of su beffective rhTNF-alpha. Food intake was decreased on the first rhIL-1 alpha infusion day because of a decreased meal number during the dark phase. A significant decrease in food intake occurred with combined in fusion of rhIL-1 alpha + rhTNF-alpha because of a reduction in meal nu mber during dark phase and meal size during light phase. Our results s how that rhIL-1 alpha and rhTNF-alpha, when administered concurrently, had a synergistic effect in inducing anorexia, suggesting that low co ncentrations of these cytokines as produced endogenously may have pote ntial effects on other biological functions in vivo.