Social stress increases the susceptibility to endotoxic shock

The influence of social disruption stress (SDR) on the susceptibility to en dotoxic shock was investigated. SDR was found to increase the mortality of mice when they were challenged with the bacterial endotoxin lipopolysacchar ide (LPS). Histological examination of SDR animals after LPS injection reve aled widespread disseminated intravascular coagulation in the brain and lun g, extensive meningitis in the brain. severe hemorrhage in the lung, necros is in the liver, and lymphoid hyperplasia in the spleen, indicating inflamm atory organ damage. In situ hybridization histochemical analysis showed tha t the expression of the glucocorticoid receptor mRNA was down-regulated in the brain and spleen of SDR animals while the ratio of expression of AVP/CR H-the two adrenocorticotropic hormone secretagogue, increased. After LPS in jection, the expression of pro-inflammatory cytokines, IL-1 beta and TNF-al pha, was found significantly higher in the lung, liver, spleen, and brain o f the SDR mice as compared with the LPS-injected home cage control animals. Taken together, these results show that SDR stress increases the susceptib ility to endotoxic shock and suggest that the development of glucocorticoid resistance and increased production of pro-inflammatory cytokines are the mechanisms for this behavior-induced susceptibility to endotoxic shock. (C) 2001 Elsevier Science B.V. All rights reserved.