How the immune and nervous systems interact during disease-associated anorexia

Anorexia is one of the most common symptoms associated with illness and con stitutes an adaptive strategy in fighting acute infectious diseases. Howeve r, prolonged reduction in food intake and an increase in metabolic rate, as seen in the anorexia-cachexia syndrome, lead to depletion of body fat and protein reserves, thus worsening the organism's condition. Because the cent ral nervous system controls many aspects of food intake, soluble factors kn own as cytokines that are secreted by immune cells might act on the brain t o induce anorexia during disease. This review focuses on the communication pathways from the immune system to the brain that might mediate anorexia du ring disease. The vagus nerve is a rapid route of communication from the im mune system to the brain, as subdiaphragmatic vagotomy attenuates the decre ase in food-motivated behavior and c-Fos expression in the central nervous system in response to peripheral administration of the proinflammatory cyto kine, interleukin-1 beta, or bacterial Lipopolysaccharide. At later time po ints after peripheral lipopolysaccharide administration, interleukin-1 itse lf acts in the brain to mediate anorexia and is found in the arcuate nucleu s of the hypothalamus. The mechanisms by which interleukin-1 beta gains acc ess to the brain and the potential role of neuropeptide-Y-containing neuron s in the arcuate hypothalamus in mediating anorexia during disease are disc ussed. (C) Elsevier Science Inc. 2001.