Beta-adrenoceptor-induced inhibition of rat splenocyte proliferation: cytokine gene transcription as the target of action.
Recently, we have demonstrated that behavioral conditioning reduced splenocyte proliferation and IL-2 production in DA rats, and that these behaviorally conditioned immunosuppressive effects were completely abrogated by prior surgical denervation of the spleen. Since the splenic denervation significantly reduced catecholamine concentrations in the spleen, adrenergic mechanisms have been considered to play an important role in conditioned immunosuppression observed in this model. Thus, the current in vitro studies were designed to analyze the influence of adrenergic mechanisms on the proliferation of rat splenocytes, their IL-2 production, and IL-2 mRNA expression. The data demonstrate that beta-adrenoceptor agonist isoproterenol at concentrations of 10(-5) M diminished mitogen (ConA)-induced splenocyte proliferation by 75%, which was associated with a pronounced (50%) decrease in IL-2 production at both the protein and mRNA levels. The beta-adrenoceptor antagonist propranolol completely reversed the isoproterenol-mediated suppressive effects. Stimulation of splenocytes with the mitogen and either the alpha1-adrenoceptor agonist methoxamine or the alpha2-adrenoceptor agonist UK-14,304 did not affect splenocyte proliferation, IL-2 synthesis or IL-2 mRNA expression. These data demonstrate that catecholamines inhibit splenocyte proliferation and IL-2 production via a beta-adrenoceptor-induced regulation of IL-2 mRNA expression, indicating that beta-adrenoceptor mechanisms are responsible for behaviorally conditioned immunosuppression.
Xie
Yufen
Y
Department of Medical Psychology, University of Essen, Germany.
Frede
Stilla
S
Harnish
Michael J
MJ
Exton
Michael S
MS
Schedlowski
Manfred
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D003208:Concanavalin A / Q000494:pharmacology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D007545:Isoproterenol / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000294:innervation / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D007376:Interleukin-2; D011810:Quinoxalines; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D003208:Concanavalin A; D000068438:Brimonidine Tartrate; D008729:Methoxamine; D007545:Isoproterenol