Contribution of differently localized alpha 2- and beta-adrenoceptors in the modulation of TNF-alpha and IL-10 production in endotoxemic mice.

Evidence is presented that the immune response to endotoxemia is under tonic control of the sympathetic nervous system. Adrenergic agents may influence the immune response both directly through alpha- and beta-adrenergic receptors expressed by immunologically competent cells and indirectly via alteration of the endogenous NA level by influencing the activity of release-regulating presynaptic alpha 2-adrenoceptors located on the sympathetic nerve terminals. In the immunomodulatory effect of NA/adrenergic drugs, their action on beta-adrenoceptors was dominant, but the considerable role of alpha-adrenoceptors on macrophages was also demonstrated. According to our findings, regulation of the ascending wing of the inflammatory response, that is, TNF-alpha production, is more sensitive to the adrenoceptor effect, whereas modulation of its deregulation by IL-10 production also involves some other determining factors.