Ciliary neurotrophic factor and leptin induce distinct patterns of immediate early gene expression in the brain

Ciliary neurotrophic factor (CNTF) and leptin decrease food intake and body weight. Lipopolysaccharide (LPS) is a potent exogenous pyrogen and produces anorexia via cytokine production. CNTF-, leptin-, and LPS-induced cytokines all act on type I cytokine receptors. However, it is not known if these cytokines engage similar central nervous system (CNS) pathways to exert their effects. To assess mechanisms by which these cytokines act, we examined the patterns of immediate early gene expression (SOCS-3, c-fos, and tis-11) in the brain following intravenous administration. CNTF and LPS induced gene expression in circumventricular organs; ependymal cells of the ventricles, meninges, and choroid plexus; and the arcuate nucleus of the hypothalamus. CNTF administration also induced fever and cyclooxygenase-2 mRNA expression. In contrast, we found no evidence of leptin-induced inflammation. CNTF and leptin are being assessed as potential therapeutic anti-obesity agents, and both potently reduce food intake. Our findings support the hypothesis that CNTF and leptin engage distinct CNS sites and CNTF possesses inflammatory properties distinct from leptin.