Restraint stress-induced immunosuppression by inhibiting leukocyte migration and Th1 cytokine expression during the intraperitoneal infection of Listeria monocytogenes

In this study, a murine model of Listeria monocytogenes infection was used to investigate effects of restraint stress (RST) on host defense. We observ ed that the L. monocytogenes infection as well as RST induced an elevation of endogenous corticosterone (CORT) levels and RST synergistically enhanced endogenous CORT levels during the listerial infection. RST suppressed the migration of leukocytes including macrophages, neutrophils, NK cells and ly mphocytes into the peritoneal cavities after the intraperitoneal inoculatio n of L. monocytogenes. RST also suppressed the increase of the surface MHC class II antigen expression in both peritoneal macrophages and B cells duri ng the listerial infection. Interestingly, gene expression of iNOS, MCP-1 ( JE) and Th1-type cytokines including IFN-gamma and IL-12 was down-regulated but Th2-type cytokine (IL-4 and IL-6) gene expression in the PEC was rathe r up-regulated on day 7 after infection, indicating that Th2-type immune re sponse is more resistant to the elevated endogenous CORT levels than Th1-ty pe response. Treatment of mice with RU486, a glucocorticoid receptor antago nist, restored the immune responses suppressed by RST to their normal level s in the infected mice, suggesting that the RST-induced elevation of endoge nous corticosterone levels is mainly responsible for the induction of the i mmunosuppressive events during L. monocytogenes infection. (C) 1998 Elsevie r Science B.V. All rights reserved.