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 neuroendocrine regulation of cytokine production. Restraint stress (RST) was used to activate the hypothalamic-pituitary-adrenal axis and elevate corticosterone (CORT) levels in influenza A/Puerto Rico/8/34 (PR8) virus-infected C57BL/6 mice. The type II glucocorticoid receptor antagonist RU486 was used to specifically examine the modulation of PR8 virus-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 addition, 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 by CORT. Furthermore, CORT was shown to inhibit the PR8 virus-specific production of both Thl-type and Th2-type cytokines in vitro at doses corresponding to the physiologic range of free plasma CORT following hypothalamic-pituitary-adrenal axis activation.
Dobbs
C M
CM
Department of Medical Microbiology and Immunology, College of Medicine, Ohio State University, Columbus 43210, USA.
Feng
N
N
Beck
F M
FM
Sheridan
J F
JF
D000305:Adrenal Cortex Hormones / Q000502:physiology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D009980:Influenza A virus / Q000276:immunology; D008206:Lymphatic Diseases / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D009490:Neurosecretory Systems / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D012149:Restraint, Physical; D013154:Spleen / Q000473:pathology; D013234:Stem Cells; D013312:Stress, Physiological / Q000276:immunology*; D018417:Th1 Cells / Q000378:metabolism / Q000821:virology; D018418:Th2 Cells / Q000378:metabolism / Q000821:virology
D000305:Adrenal Cortex Hormones; D016207:Cytokines; D015735:Mifepristone