NEUROENDOCRINE REGULATION OF CYTOKINE PRODUCTION DURING EXPERIMENTAL INFLUENZA VIRAL-INFECTION - EFFECTS OF RESTRAINT STRESS-INDUCED ELEVATION IN ENDOGENOUS CORTICOSTERONE

A murine model of influenza viral infection was used to examine the ne uroendocrine regulation of cytokine production. Restraint stress (RST) was used to activate the hypothalamic-pituitary-adrenal axis and elev ate corticosterone (CORT) levels in influenza A/Puerto Rico/8/34 (PR8) virus-infected C57BL/6 mice. The type II glucocorticoid receptor anta gonist RU486 was used to specifically examine the modulation of PR8 vi rus-specific cytokine responses by CORT. RST suppressed the PR8 virus- specific production of th1-type (IL-2 and IFN-gamma) and Th2-type (IL- 10) cytokines by cells from the regional lymph nodes and spleens, In a ddition, IL-6 production by splenocytes was inhibited by RST; however, IL-6 production by cells from the regional lymph nodes was enhanced, Treatment of mice with RU486 prevented the effects of RST, suggesting that the RST-induced alterations in cytokine responses were mediated b y CORT, Furthermore, CORT was shown to inhibit Be PR8 virus-specific p roduction of both Th1-type and Th2-type cytokines in vitro at doses co rresponding to the physiologic range of free plasma CORT following hyp othalamic-pituitary-adrenal axis activation.