Research indicates that psychological stress can modulate immune responses. Here we demonstrate that restraint stress suppresses interferon (IFN)-γ production and signalling in mice following in vivo lipopolysaccharide (LPS) treatment. Stress also suppressed production of the IFN-γ inducing cytokine interleukin (IL)-12 and increased production of the anti-infl ammatory cytokine IL-10, which can inhibit both IL-12 and IFN-γ production. Studies with IL-10 knockout mice demonstrate that IL-10 does not mediate the suppressive effect of stress on IFN-γ production. Consistent with a role for glucocorticoids in the immunosuppressive actions of stress, the glucocorticoid receptor antagonist mifepristone blocked the stress-related suppression of IFN-γ. In contrast, the stress-induced increase in IL-10 was blocked by the beta-adrenergic receptor antagonist nadolol. Addition of IL-12 to LPS-stimulated spleen cells reversed the suppressive effect of stress and corticosterone on IFN-γ production, suggesting that reduced IL-12 production is a key event in stress-induced suppression of IFN-γ production. Finally, we demonstrate that treatment with the anxiolytic drug chlordiazepoxide prevents the ability of stress to increase IL-10 and suppress IFN-γ production.
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