Acute stress suppresses pro-inflammatory cytokines TNF-α and IL-1β independent of a catecholamine-driven increase in IL-10 production

Interleukin (IL)-10 is an anti-inflammatory cytokine that can down-regulate various aspects of the immune response. In this study we demonstrate that exposure to a psychophysiological stressor (swim stress) increases IL-10 production in female rats in response to an in vivo challenge with bacterial lipopolysaccharide (LPS). This increase in LPS-induced IL-10 was associated with suppression of the pro-inflammatory cytokines IL-1β and TNF-α, indicating that overall, swim stress promotes an immunosuppressive cytokine phenotype. Despite the well-documented ability of IL-10 to suppress pro-inflammatory cytokine production, neutralisation of IL-10 failed to block the stress-induced suppression of IL-1β and TNF-α. These data indicate that the suppressive effect of swim stress on these pro-inflammatory cytokines occurs independently of increased IL-10 production. To determine if swim stress-induced immunosuppression was mediated by increased sympathetic nervous system activity, and subsequent β-adrenoceptor activation, we assessed the ability of the β-adrenoceptor antagonist nadolol to block stressor-induced changes in cytokine production. Whilst pre-treatment with nadolol completely blocked the stress-induced increase in IL-10, it failed to alter the suppression of TNF-α or IL-1β. Similarly, pre-treatment with the glucocorticoid receptor antagonist mifepristone also failed to attenuate the suppressive effect of swim stress on IL-1β and TNF-α production. These data indicate that neither increased glucocorticoid secretion, nor catecholamine-induced β-adrenoceptor activation, mediates the suppressive effect of swim stress on pro-inflammatory cytokine production. Taken together, these data demonstrate a role for β-adrenoceptor activation in the ability of acute swim stress to increase LPS-induced IL-10 production, and also highlight a mechanistic dissociation between the ability of swim stress to increase IL-10 and suppress pro-inflammatory cytokine production.