Interleukins and tumor necrosis factor as inhibitors of food intake

Cytokines, such as interleukins and tumor necrosis factor-alpha (TNF alpha) , are produced in response to immune stimulation and have systemic effects, mediated by the central nervous system (CNS). Interleukins, in particular interleukin [IL]-1 beta, and TNF alpha reduce food intake after peripheral and central administration, suggesting that they contribute to the anorexia during various infectious, neoplastic and autoimmune diseases. Because cyt okines are mainly produced in the periphery during most of these diseases, IL-1 beta and TNF alpha may inhibit feeding indirectly through neural and h umoral pathways activated by their peripheral actions. Activation of affere nt nerve fibers by locally produced cytokines in the periphery is involved in several cytokine effects, but is not crucial for the anorectic effect of systemic immune stimulation. Cytokines increase OB protein (leptin) expres sion in the adipose tissue, and leptin may contribute to, but is also not e ssential for, the anorectic effects of cytokines. Finally, circulating IL-1 beta and TNF alpha may act directly on the brain or cytokine synthesis in the brain may contribute to the anorectic effect of systemic immune stimula tion. Central mediators of the anorectic effects of cytokines appear to be neurochemicals involved in the normal control of feeding, such as serotonin , corticotropin releasing factor, histamine, a-melanocyte stimulating hormo ne, and neuropeptide Y. The well-documented cytokine production in the gut in relation to feeding and the expression of TNF alpha by adipocytes sugges t that IL-1 beta and TNF alpha may also play a role in the control of norma l feeding and energy balance. All in all, reciprocal, synergistic and antag onistic interactions between various pleiotropic cytokines and between cyto kines and neurochemicals form a complex network that mediates the effects o f cytokines on feeding and energy balance. (C) 1999 Harcourt Publishers Ltd .