Acute stress suppresses pro-inflammatory cytokines TNF-alpha and IL-1 beta 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-1beta and TNF-alpha, 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-1beta and TNF-alpha. 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 beta-adrenoceptor activation, we assessed the ability of the beta-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-alpha or IL-1beta. Similarly, pre-treatment with the glucocorticoid receptor antagonist mifepristone also failed to attenuate the suppressive effect of swim stress on IL-1beta and TNF-alpha production. These data indicate that neither increased glucocorticoid secretion, nor catecholamine-induced beta-adrenoceptor activation, mediates the suppressive effect of swim stress on pro-inflammatory cytokine production. Taken together, these data demonstrate a role for beta-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.
Connor
Thomas J
TJ
Department of Physiology, Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland. connort@tcd.ie
Brewer
Charlene
C
Kelly
John P
JP
Harkin
Andrew
A
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002395:Catecholamines / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D005260:Female; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D009248:Nadolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D013315:Stress, Psychological / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
D000319:Adrenergic beta-Antagonists; D019138:Antibodies, Blocking; D002395:Catecholamines; D018836:Inflammation Mediators; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015735:Mifepristone; D009248:Nadolol