Cytokine-induced sickness behavior: Where do we stand?

Sickness behavior refers to the coordinated set of behavioral changes that develop in sick individuals during the course of an infection. At the molec ular level, these changes are due to the effects of proinflammatory cytokin es, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF alpha ), in the brain. Peripherally released cytokines act on the brain via a fas t transmission pathway involving primary afferent nerves innervating the bo dy site of inflammation and a slow transmission pathway involving cytokines originating from the choroid plexus and circumventricular organs and diffu sing into the brain parenchyma by volume transmission. At the behavioral le vel, sickness behavior appears to be the expression of a central motivation al state that reorganizes the organism's priorities to cope with infectious pathogens. There is clinical and experimental evidence that activation of the brain cytokine system is associated with depression, although the exact relationship between sickness behavior and depression is still elusive. (C ) 2001 Academic Press.