Cytokine-Associated Emotional and Cognitive Disturbances in Humans

Top Cited Papers
Open Access
Publisher Website
Google Scholar
Abstract
INFECTIOUS DISEASES are associated with profound behavioral disturbances. These are collectively termed sickness behavior (SB) and include malaise, fatigue, depression, anorexia, hyposomnia or hypersomnia, decreased physical and social activities, and cognitive disturbances.1-3 Several lines of evidence suggest that inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-1, and IL-6, meditate these disturbances. In animals, SB can be induced by administration of cytokines, and antagonists or synthesis blockers of cytokines abolish SB in response to various immune challenges.2-5 Studies in humans indicate that administration of cytokines (particularly interferons and IL-2) produces behavioral alterations similar to SB in animals, as well as depressive symptoms and impairments of memory, attention, and executive functions.6-10 However, these studies are limited because of 2 major reasons: (1) In general, effects of cytokines have been studied in severely ill patients, and thus may add to or interfere with different preexisting medical and psychological conditions. (2) The high doses that have been administered induce prominent physical sickness symptoms that by themselves are likely to compromise cognitive performance and the patients' emotional condition. Therefore, it is desirable to investigate the emotional and cognitive effects of experimental immunostimulation in healthy subjects.