title: Psychological stress increases expression of IL-10 and its homolog IL-19 via beta-adrenoceptor activation: reversal by the anxiolytic chlordiazepoxide.
abstract: Recent studies from our laboratory indicate that psychological stress is a potent inducer of the anti-inflammatory cytokine interleukin (IL)-10, raising the possibility that the IL-10 family of cytokines may be key mediators of stress-induced immunosuppression. In this study we examined the impact of psychological stress (restraint stress) on expression of IL-10, and the novel IL-10 family members IL-19, IL-20 and IL-24 in mouse spleen following an in vivo challenge with lipopolysaccharide (LPS). We found that stressor exposure significantly augmented LPS-induced IL-10 expression. Similarly, IL-19 expression was induced by LPS, and this was significantly enhanced by restraint stress. In contrast, expression of IL-24 was not significantly altered by LPS or stress, and expression of IL-20 was largely not detectable in vivo in either saline or LPS-treated animals. Consistent with a role for sympathetic nervous system (SNS) activation in stress-induced immune regulation, the sympathetic neurotransmitter noradrenaline increased LPS-induced IL-10 and IL-19 expression in splenocytes and dendritic cells, and the ability of noradrenaline to induce expression of these cytokines was blocked by pre-treatment with the beta-adrenoceptor antagonist propranolol. Similarly, pre-treatment of mice with the peripherally acting beta-adrenoceptor antagonist nadolol completely blocked the stress-induced increase in IL-10 and IL-19 mRNA expression. Finally, pre-treatment with the benzodiazepine anxiolytic chlordiazepoxide prevented the stress-induced increase in IL-10 and IL-19 expression. Taken together, these data demonstrate that psychological stress induces expression of the IL-10 and its homolog IL-19 via activation of beta-adrenoceptors, and the ability of stress to induce these cytokines is prevented by treatment with the anxiolytic chlordiazepoxide. The findings suggest that stress enhances the production of immunosuppressive cytokines, which may impact on stress-related disease processes.
authors.affiliation: Neuroimmunology Research Group, Department of Physiology, School of Medicine & Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland.
authors.forename: Niamh M
authors.initials: NM
authors.lastname: Curtin
authors.forename: Kingston H G
authors.initials: KH
authors.lastname: Mills
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Connor
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000008:administration & dosage / Q000494:pharmacology*; D003713:Dendritic Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009248:Nadolol / Q000008:administration & dosage / Q000494:pharmacology; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000097:blood; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism; D013315:Stress, Psychological / Q000276:immunology* / Q000378:metabolism; D000099180:Interleukin-24
chemical_list: D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D001569:Benzodiazepines; D002707:Chlordiazepoxide; D016753:Interleukin-10; D007378:Interleukins; D008070:Lipopolysaccharides; D009248:Nadolol; D009638:Norepinephrine; D011433:Propranolol; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D000099180:Interleukin-24; C498891:Il19 protein, mouse; C422042:interleukin 20