Objective: The purpose of this study is to assess the role of psychological
stress in the expression of illness among infected subjects and to test th
e plausibility of local proinflammatory cytokine production as a pathway li
nking stress to illness. Methods: After completing a measure of psychologic
al stress, 55 subjects were experimentally infected with an influenza A vir
us. Subjects were monitored in quarantine daily for upper respiratory Sympt
oms, mucus production, and nasal lavage levels of interleukin (IL)-6. Resul
ts: Higher psychological stress assessed before the viral challenge was ass
ociated with greater symptom scores, greater mucus weights, and higher IL-6
lavage concentrations in response to infection. The IL-6 response was temp
orally related to the two markers of illness severity, and mediation analys
es indicated that these data were consistent with IL-6 acting as a major pa
thway through which stress was associated with increased symptoms of illnes
s. However, this pattern of data is also consistent with increases in IL-6
occurring in response to tissue damage associated with illness symptoms. Co
nclusions: Psychological stress predicts a greater expression of illness an
d an increased production of IL-6 in response to an upper respiratory infec
tion.