Social disruption, immunity, and susceptibility to viral infection. Role of glucocorticoid insensitivity and NGF.
Glucocorticoid (cort) responses have been shown to suppress inflammatory reactions by inhibiting the trafficking of immune cells. Recently, it was demonstrated that restraint stress (RST) and psychosocial stress (social reorganization; SRO) differentially affected the pathophysiology and survival in the mouse influenza viral infection model. While both stressors activated the HPA axis, only SRO affected survival. In RST, elevated cort diminished recruitment of inflammatory cells following intranasal challenge of C57BL/6 mice with A/PR8 virus. However, infected SRO mice developed hypercellularity in the lungs and were more likely to die from lung consolidation than controls. Since elevated cort failed to be anti-inflammatory in SRO mice, the hypothesis that psychosocial stress induced steroid insensitivity was tested. An in vitro cort suppression test was performed by stimulating splenocytes from SRO and control mice with mitogen in the presence or absence of cort. Proliferation of ConA-stimulated cells was inhibited by cort in a dose-dependent fashion in controls, but splenocytes from SRO mice stimulated with ConA were resistant to cort-induced suppression. Thus, psychosocial stress induced a state of steroid insensitivity. SRO also induced the release of nerve growth factor (NGF) from the salivary glands into circulation; plasma NGF correlated with development of steroid insensitivity. NGF has been reported to negatively regulate the expression of type II glucocorticoid receptors, and thus may be a key factor in the induction of steroid insensitivity.
Laboratory of Neuroendocrine Immunology, Section of Oral Biology, College of Dentistry, Institute for Behavioral Medicine Research, Ohio State University Health Sciences Center, 305 W.12th Ave., Columbus, OH 43210, USA.
J F
JF
Sheridan
J L
JL
Stark
R
R
Avitsur
D A
DA
Padgett
D000818:Animals; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005938:Glucocorticoids / Q000276:immunology*; D007109:Immunity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000276:immunology*; D013315:Stress, Psychological / Q000276:immunology*; D014777:Virus Diseases / Q000209:etiology / Q000276:immunology*
D005938:Glucocorticoids; D020932:Nerve Growth Factor