Differential involvement of sympathetic nervous system and immune system in the modulation of TNF- alpha production by alpha sub(2)- and beta -adrenoceptors in mice

In the present study, the regulation of tumor necrosis factor- alpha (TNF- alpha ) production by alpha sub(2)- 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 alpha sub(2)-adrenoceptors, was a determinant factor in this model. By using alpha sub(2)- and beta -adrenergic drugs (clonidine, CH-38083, isoproterenol, propranolol) we provided the first in vivo evidence that, beside the dominance of neuronal alpha sub(2)- and macrophage beta -adrenoceptors, the alpha sub(2)-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.