STRESS-INDUCED GLUCOCORTICOID RESPONSE MODULATES MONONUCLEAR CELL TRAFFICKING DURING AN EXPERIMENTAL INFLUENZA VIRAL-INFECTION

The migration, distribution, and localization of lymphoid cells throug hout the body is critical to the efficiency and development of the imm une response. This study examined the role of endogenous glucocorticoi ds 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 dev elopment of the immune response. PR8-infected mice demonstrated an ele vation in circulating corticosterone regardless of whether they were t reated with RU486 or a placebo. Thus, some 'afferent' signal associate d with the infection, and/or the immune response to infection, activat ed the hypothalamic-pituitary-adrenal axis (HPA) and was not subject t o negative feedback regulation. The initial accumulation of MNC in the draining lymph nodes and lungs during infection, however, was indepen dent of the glucocorticoid response. Our previous studies demonstrated that virally infected animals subjected to physical restraint had hig hly elevated plasma corticosterone levels, suppressed lymphadenopathy, and reduced accumulation of MNC in the lungs. In the present study, R U486 treatment restored cellularity to the draining lymph nodes and en hanced accumulation of MNC in lungs of stressed, A/PR8 virus-infected mice.