Cytokine-Induced Sickness Behavior: Mechanisms and Implications

ABSTRACT: Sickness behavior refers to a 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 brain effects of proinflammatory cyto-kines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF). Peripherally released cytokines act on the brain via a fast transmission path-way involving primary afferent nerves innervating the bodily site of inflamma-tion and a slow transmission pathway involving cytokines originating from the choroid plexus and circumventricular organs and diffusing into the brain parenchyma by volume transmission. At the behavioral level, sickness behavior appears to be the expression of a central motivational state that reorganizes the organism priorities to cope with infectious pathogens. There is evidence that the sickness motivational state can interact with other motivational states and respond to nonimmune stimuli probably by way of sensitization and/or classi-cal conditioning. However, the mechanisms that are involved in plasticity of the sickness motivational state are not yet understood