Cytokine-induced anorexia. Behavioral, cellular, and molecular mechanisms.

Abstract

Cytokines induce anorexia. Recent issues concerning mechanistic aspects are: (1) Cytokines induce anorexia through different modes of behavioral action, that is, by affecting meal size, meal duration, and meal frequency differentially. Profiles also depend on the concentration or dosage. (2) The interface between the periphery and brain. Specific cytokines may be transported from the periphery to the brain. Cytokines generate mediators that can act on peripheral and/or brain target sites. Cerebrovasculature endothelium can also generate signals to modulate neural activities. Evidence indicates that the proposed vagal afferent signaling requires reassessment. Because of paracrine and autocrine actions, local cytokine production within the brain can induce anorexia. (3) Cytokines act directly on hypothalamic neurons proposed to participate in feeding. (4) Cytokine<-->cytokine and cytokine<-->peptide/neurotransmitter interactions are critical; for example, cytokines interact to induce anorexia synergistically, neuropeptide Y<-->cytokine interactions are antagonist, and cytokine<-->neurotransmitter and cytokine<-->leptin<-->neuropeptide Y<-->CRH-glucocorticoid and other endocrine interactions are important. A leptin receptor is related to gp 130, a signal transducer among interleukin (IL)-6 subfamily receptors; gp 130 and related molecules may be an interface for feeding control in health and disease. Various cytokines upregulate leptin and gp 130. An integrative approach combining computerized meal pattern analyses with cellular and molecular approaches is being used to characterize mechanisms (ligands, receptors, transducing molecules, and intracellular mediators) involved in cytokine-induced anorexia.