Stimulation of beta-adrenoceptors inhibits endotoxin-induced IL-12 production in normal and IL-10 deficient mice.
Stimulation of beta-adrenoceptors has been shown to regulate the production of various inflammatory mediators. In the present study, we investigated in mice whether ligation of beta-adrenoceptors, modulates lipopolysaccharide (LPS)-induced plasma levels of interleukin (IL)-12, interferon-gamma (IFN-gamma), and IL-10. In BALB/c mice, isoproterenol (1-10 mg kg(-1) , i.p.), a selective agonist of beta-adrenoceptors and also dexamethasone (10 mg kg(-1), i.p.) pretreatment 30 min before the administration of LPS suppressed plasma IL-12 (p40 and p70) concentrations as determined at various time points after the LPS challenge. The inhibition of IL-12 release by isoproterenol was prevented by the beta-adrenoceptor antagonist propranolol confirming the involvement of beta-adrenoceptors in the effect of isoproterenol. Furthermore, pretreatment of the animals with propranolol alone enhanced LPS-induced plasma IL-12, suggesting that endogenous catecholamines inhibit IL-12 production via the beta-adrenoceptors. In IL-10 deficient C57BL/6 IL-10(-/-) mice, plasma levels of IL-12 and IFN-gamma were significantly higher than in their counterparts, with more than 70-fold increase in IL-12. Furthermore, while augmenting the IL-10 response in C57BL/6 IL-10(+/+), isoproterenol inhibited the production of IL-12 in both the C57BL/6 IL-10(+/+) and C57BL/6 IL-10(-/-) mice, suggesting that the inhibition of IL-12 production by this compound is independent of the increased release of IL-10. Our results demonstrate, for the first time, that stimulation of beta-adrenoceptors by isoproterenol or endogenous catecholamines suppresses IL-12 production in vivo.
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
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Haskó
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Szabó
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Németh
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Salzman
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Vizi
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D016753:Interleukin-10 / Q000172:deficiency*; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000097:blood; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012016:Reference Values
D000318:Adrenergic beta-Agonists; D004731:Endotoxins; D011943:Receptors, Adrenergic, beta; D016753:Interleukin-10; D018664:Interleukin-12; D007545:Isoproterenol