Seasonal variations in inflammatory responses to sepsis and stress in mice

Objective: In this study, we analyzed seasonal variations of immunoreactivity using a model of septic shock and a model of immunosuppression induced by chronic stress in mice. Design: Retrospective comparative study using animals of experiments performed between 2001 and 2006 to identify seasonal variations in inflammatory responsiveness of mice. Setting: University-based research laboratory. Subjects: C57BI/6 mice and BALB/c mice. Interventions: For analyzing septic shock, we used the hyperinflammatory model of colon ascendens stent peritonitis. Immunosuppression was induced by 4.5 days of intermittent combined acoustic and restraint stress. Measurements and Main Results: We show that mice kept with 12:12-hr light/dark rhythm had an enhanced risk to die of experimentally-induced hyperinflammatory peritonitis performed in summer or autumn compared with the other seasons. This finding was associated with an exaggerated proinflammatory response of C57BI/6 mice in summer or autumn compared with moderate inflammatory reactivity in winter and spring. Consistent with these results, we report that the severity of a stress-induced immunosuppression is less pronounced in BALB/c mice that were exposed to chronic psychological stress in the summer compared with exposure in winter. Coping with chronic psychological stress of these animals was correlated with less pronounced corticosterone release, less severe lymphocytopenia, and a lower ex vivo inducibility of interluekin-10, thereby attenuating a stress-mediated immunosuppressive state. Mice subjected to chronic stress in the summer season showed increased coping compared with mice that were stressed in the winter season. Conclusions: Our results suggest that seasonal changes of the host's hypothalamus-pituitary-adrenal axis response influence the risk of infection and the susceptibility to stress, which interferes with the outcome after infection.