Interleukins and tumor necrosis factor as inhibitors of food intake

Cytokines, such as interleukins and tumor necrosis factor-alpha (TNFalpha), are produced in response to immune stimulation and have systemic effects, mediated by the central nervous system (CNS). Interleukins, in particular interleukin [IL]-1beta, and TNFalpha reduce food intake after peripheral and central administration, suggesting that they contribute to the anorexia during various infectious, neoplastic and autoimmune diseases. Because cytokines are mainly produced in the periphery during most of these diseases, IL-1beta and TNFalpha may inhibit feeding indirectly through neural and humoral pathways activated by their peripheral actions. Activation of afferent 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) expression in the adipose tissue, and leptin may contribute to, but is also not essential for, the anorectic effects of cytokines. Finally, circulating IL-1beta and TNFalpha may act directly on the brain or cytokine synthesis in the brain may contribute to the anorectic effect of systemic immune stimulation. 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, alpha-melanocyte stimulating hormone, and neuropeptide Y. The well-documented cytokine production in the gut in relation to feeding and the expression of TNFalpha by adipocytes suggest that IL-1beta and TNFalpha may also play a role in the control of normal feeding and energy balance. All in all, reciprocal, synergistic and antagonistic interactions between various pleiotropic cytokines and between cytokines and neurochemicals form a complex network that mediates the effects of cytokines on feeding and energy balance.

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