Social stress increases the susceptibility to endotoxic shock

Ning Quan, Ronit Avitsur, Jennifer L. Stark, Lingli He, Manisha Shah, Michael Caligiuri, David A. Padgett, Phillip T. Marucha, John F. Sheridan

Research output: Contribution to journalArticlepeer-review

141 Scopus citations

Abstract

The influence of social disruption stress (SDR) on the susceptibility to endotoxic shock was investigated. SDR was found to increase the mortality of mice when they were challenged with the bacterial endotoxin lipopolysaccharide (LPS). Histological examination of SDR animals after LPS injection revealed widespread disseminated intravascular coagulation in the brain and lung, extensive meningitis in the brain, severe hemorrhage in the lung, necrosis in the liver, and lymphoid hyperplasia in the spleen, indicating inflammatory organ damage. In situ hybridization histochemical analysis showed that 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/CRH-the two adrenocorticotropic hormone secretagogue, increased. After LPS injection, the expression of pro-inflammatory cytokines, IL-1β and TNF-α, was found significantly higher in the lung, liver, spleen, and brain of the SDR mice as compared with the LPS-injected home cage control animals. Taken together, these results show that SDR stress increases the susceptibility 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.

Original languageEnglish (US)
Pages (from-to)36-45
Number of pages10
JournalJournal of Neuroimmunology
Volume115
Issue number1-2
DOIs
StatePublished - Apr 2 2001

Keywords

  • Depression
  • Glucocorticoid resistance
  • Inflammatory cytokines
  • Sepsis
  • Social stress

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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