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Infection commonly triggers nonspecific psychological and behavioral changes including fatigue and malaise, anhedonia, inability to concentrate, and disturbed sleep that collectively are termed “sickness behaviors”. Converging evidence from several lines of research implicate the activities of proinflammatory cytokines as a cause of sickness behaviors. Here we elaborate upon the findings of previous research by examining whether infection-associated elevations in local proinflammatory cytokines are associated with increased negative mood and decreased positive mood. One hundred and eighty-nine healthy adults were experimentally exposed to rhinovirus or influenza virus during a 6-day period of quarantine. Infection, objective signs of illness, nasal IL-1β, IL-6, and TNF-α, and self-reported affect were assessed at baseline and on each of the five post-challenge quarantine days. In the 153 persons who …