Psychological stress suppresses innate IFN-γ production via glucocorticoid receptor activation: Reversal by the anxiolytic chlordiazepoxide

Abstract Studies in humans and in animals indicate that psychological stress can modulate immune responses. Here we demonstrate that exposure to psychological stress (restraint stress) suppresses innate interferon (IFN)-γ production in mice following an in vivo lipopolysaccharide (LPS) challenge. IF...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Brain, behavior, and immunity behavior, and immunity, 2009-05, Vol.23 (4), p.535-547
Hauptverfasser: Curtin, Niamh M, Boyle, Noreen T, Mills, Kingston H.G, Connor, Thomas J
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Abstract Studies in humans and in animals indicate that psychological stress can modulate immune responses. Here we demonstrate that exposure to psychological stress (restraint stress) suppresses innate interferon (IFN)-γ production in mice following an in vivo lipopolysaccharide (LPS) challenge. IFN-γ signaling was also impaired by stress, as indicated by reduced STAT1 phosphorylation and reduced expression of the IFN-γ-inducible genes, inducible nitric oxide synthase (iNOS) and IFN-γ-inducible protein 10 (IP-10/CXCL10). Furthermore, restraint stress suppressed production of the IFN-γ inducing cytokine interleukin (IL)-12 and increased production of the anti-inflammatory cytokine IL-10, which can inhibit both IL-12 and IFN-γ production. However, using IL-10 knockout mice, we demonstrate that IL-10 does not mediate the suppressive effect of restraint stress on innate IFN-γ production. Restraint stress increased corticosterone concentrations in serum and spleen, and consistent with a role for glucocorticoids in the immunosuppressive actions of stress, pre-treatment with the glucocorticoid receptor antagonist mifepristone completely blocked the stress-related suppression of innate IFN-γ production. Addition of exogenous IL-12 to LPS-stimulated spleen cells reversed the suppressive effect of both restraint stress and corticosterone on IFN-γ production. These data suggest that reduced IL-12 production is a key event in stress-induced suppression of innate IFN-γ production. Finally, we demonstrate that pre-treatment with the anxiolytic drug chlordiazepoxide prevents the suppressive effect of stress on innate IFN-γ production, and also attenuates the stress-induced increase in circulating corticosterone concentrations.
ISSN:0889-1591
1090-2139
DOI:10.1016/j.bbi.2009.02.003