期刊
PSYCHONEUROENDOCRINOLOGY
卷 33, 期 1, 页码 108-117出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.psyneuen.2007.10.007
关键词
proinflammatory cytokines; glucocorticoid resistance; social stress; spleen; lipopolysaccharide; CD11b
资金
- NIDCR NIH HHS [T32 DE014320, T32DE014320-06, T32 DE014320-07] Funding Source: Medline
- NIMH NIH HHS [R01 MH046801-15, R01 MH46801-15, R01 MH046801] Funding Source: Medline
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [T32DE014320] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH046801] Funding Source: NIH RePORTER
Frequent or chronic stress as a result of repeated or persistent exposure to social challenges has been shown to affect the glucocorticoid (GC) responsiveness of immune cells in mice. Lipopolysaccharide-stimulated splenocytes of mice that were repeatedly subjected to social disruption were less sensitive to the anti-inflammatory actions of GC as evident from an increased production of pro-inflammatory cytokines and enhanced cell survival. The development of functional GC resistance was accompanied by the accumulation of GC-insensitive CD11b(+) cells in the spleen. These cells were shown to exhibit impaired nuclear translocation of the GC receptor and lack of GC-induced suppression of NF-kappa B. Similar impairments in GC receptor function have been reported after in vitro treatment of various cell lines with interleukin (IL)-1. The aim of this study was to elucidate whether IL-1 is a critical factor for the development of GC resistance in socially stressed mice. In the first experiment, we investigated if repeated social stress alters plasma levels and tissue gene expression of IL-1 alpha and IL-1 beta. It revealed that recurrent stressor exposure significantly increased splenic and hepatic mRNA expression and the plasma protein level of IL-1 beta, and hepatic mRNA expression of IL-1 alpha. In the second experiment, IL-1 receptor type 1 (IL1R1)-deficient mice were subjected to the stressor and both the tissue distribution of CD11b(+) cells and the GC sensitivity of the splenocytes were compared to wildtype mice. Mice lacking the IL1R1 exhibited adrenal hypertrophy, thymic involution, and elevated serum corticosterone levels in response to the stressor but did not show splenic accumulation of CD11b(+) cells and failed to develop GC resistance. These findings suggest that IL-1 plays a critical role in the development of the social stress-associated GC resistance in the murine spleen. (C) 2007 Elsevier Ltd. All rights reserved.
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