Differential involvement of sympathetic nervous system and immune system in the modulation of TNF-alpha production by alpha2- and beta-adrenoceptors in mice.
In the present study, the regulation of tumor necrosis factor-alpha (TNF-alpha) production by alpha2- and beta-adrenoceptors located on noradrenergic nerve terminals and on macrophages was studied in endotoxaemic mice. We found that reduction of the sympathetic outflow by reserpine dramatically increased the lipopolysaccharide (LPS)-induced TNF-alpha production, demonstrating that the release of endogenous noradrenaline (NA), controlled by presynaptic alpha2-adrenoceptors, was a determinant factor in this model. By using alpha2- and beta-adrenergic drugs (clonidine, CH-38083, isoproterenol, propranolol) we provided the first in vivo evidence that, beside the dominance of neuronal alpha2- and macrophage beta-adrenoceptors, the alpha2-adrenoceptors on macrophages were also involved in the modulation of LPS-induced TNF-alpha production. Since adrenergic drugs are widely used in the clinical practice, our findings may have therapeutical implications.
Szelényi
J
J
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Kiss
J P
JP
Vizi
E S
ES
D058647:Adrenergic alpha-2 Receptor Agonists; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D007107:Immune System / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D015213:Neuroimmunomodulation; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D058647:Adrenergic alpha-2 Receptor Agonists; D008070:Lipopolysaccharides; D018341:Receptors, Adrenergic, alpha-2; D011943:Receptors, Adrenergic, beta; D014409:Tumor Necrosis Factor-alpha; D007545:Isoproterenol; D003000:Clonidine