TY - JOUR
T1 - Social stress increases the susceptibility to endotoxic shock
AU - Quan, Ning
AU - Avitsur, Ronit
AU - Stark, Jennifer L.
AU - He, Lingli
AU - Shah, Manisha
AU - Caligiuri, Michael
AU - Padgett, David A.
AU - Marucha, Phillip T.
AU - Sheridan, John F.
N1 - Funding Information:
This study is supported by grants from the National Institutes of Health R01MH46801 and P50DE13749 (PI: J. Sheridan and N.Q. as a co-PI), and a grant from the John D. and Catherine T. MacArthur Foundation Mind–Body Network (to J.F.S.) and from the Ohio State University (to N.Q.).
PY - 2001/4/2
Y1 - 2001/4/2
N2 - 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.
AB - 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.
KW - Depression
KW - Glucocorticoid resistance
KW - Inflammatory cytokines
KW - Sepsis
KW - Social stress
UR - http://www.scopus.com/inward/record.url?scp=0035795076&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035795076&partnerID=8YFLogxK
U2 - 10.1016/S0165-5728(01)00273-9
DO - 10.1016/S0165-5728(01)00273-9
M3 - Article
C2 - 11282152
AN - SCOPUS:0035795076
SN - 0165-5728
VL - 115
SP - 36
EP - 45
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -