The effects of noradrenaline and alpha-2 adrenoceptor agents on the production of monocytic products

Abstract

There are some reports that catecholamines may modulate the production of monocytic cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFα). The present study was carried out in order to examine the effects of noradrenaline (10 −5, 10 −6 and 10 −7 M), clonidine (10 −5, 10 −6 and 10 −7 M), an α2-adrenoceptor agonist, and yohimbine (10 −5, 10 −6 and 10 −7 M), an α2-adrenoceptor antagonist, on the production of IL-6, the IL-1 receptor antagonist (IL-1RA) and TNFα by stimulated whole blood of normal humans. We measured the in vitro production of IL-6, TNFα and IL-1RA by stimulated (phytohemagglutinin+lipopolysaccharide), diluted whole blood of 16 normal volunteers. The results show that noradrenaline, 10 −5 M, significantly suppressed the production of IL-6; noradrenaline, 10 −5 and 10 −6 M, significantly suppressed the production of IL-1RA and TNFα; clonidine, 10 −5 M, significantly suppressed the production of TNFα; and yohimbine, 10 −5 and 10 −6 M, significantly suppressed the production of IL-1RA. It is concluded that (1) noradrenaline has significant negative immunoregulatory effects in humans through suppression of the production of (monocytic) proinflammatory cytokines, e.g. IL-6 and TNFα, and (2) the suppression of the production of TNFα may be related to α 2-adrenoceptor-related mechanisms.