Effects of insulin-like growth factor-I on cytokine-induced sickness behavior in mice

Central administration of insulin-like growth factor-I (IGF-T) attenuates sickness behavior in response to the cytokine inducer lipopolysaccharide. The present study was designed to determine the respective roles of the two main proinflammatory cytokines, tumor necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta), in these effects. Male CD1 mice were injected into the lateral ventricle (i.c.v) of the brain with optimal amounts of either TNF alpha (50 ng) or TL-1 beta (2 ng) that induce sickness behavior. Behavioral responses to TGF-I (0, .1, and 1 mu g) also given i.c.v. were measured at various time intervals before and after treatment with the two proinflammatory cytokines. Mice treated with TNF alpha and IL-1 beta lost body weight and displayed equivalent reductions in social exploration and instances of immobility. At the dose of 1 mu g, IGF-I attenuated these signs of sickness in TNF alpha-but not in TL-1 beta-treated mice. At the dose of 1 mu g, IGF-I attenuated IL-1 beta-induced immobility and the reduction in social exploration but had no effect on loss of body weight. These findings indicate that IGF-I is more potent in attenuating sickness behavior induced by TNF alpha than that caused by IL-1 beta. which is consistent with the relative specificity of the TNF alpha/IGF-I interactions in the brain. (c) 2005 Elsevier Inc. All rights reserved.