Stress-induced glucocorticoid response modulates mononuclear cell trafficking during an experimental influenza viral infection.

The migration, distribution, and localization of lymphoid cells throughout the body is critical to the efficiency and development of the immune response. This study examined the role of endogenous glucocorticoids in mononuclear cell (MNC) trafficking during the development of an immune response to infection by influenza A/PR8 virus. Accumulation of MNC in the draining lymph nodes and at the site of virus replication (lungs) was studied in infected mice, and infected mice subjected to a stressor (physical restraint). The glucocorticoid antagonist, RU486, was used to block the activity of endogenous corticosterone during development of the immune response. PR8-infected mice demonstrated an elevation in circulating corticosterone regardless of whether they were treated with RU486 or a placebo. Thus, some 'afferent' signal associated with the infection, and/or the immune response to infection, activated the hypothalamic-pituitary-adrenal axis (HPA) and was not subject to negative feedback regulation. The initial accumulation of MNC in the draining lymph nodes and lungs during infection, however, was independent of the glucocorticoid response. Our previous studies demonstrated that virally infected animals subjected to physical restraint had highly elevated plasma corticosterone levels, suppressed lymphadenopathy, and reduced accumulation of MNC in the lungs. In the present study, RU486 treatment restored cellularity to the draining lymph nodes and enhanced accumulation of MNC in lungs of stressed, A/PR8 virus-infected mice.