Negative immunoregulatory effects of noradrenaline through alpha2-adrenoceptor activation

BACKGROUND: There are some reports that catecholamines and beta-adrenoceptor agonists may suppress some immune functions. OBJECTIVES: The present study was carried out in order to examine the effects of noradrenaline (10-5 M, 10-6 M and 10-7 M), yohimbine (10-5 M, 10-6 M and 10-7 M), an alpha2-adrenoceptor antagonist, and clonidine (105 M, 10-6 M and 10-7 M), an alpha2-adrenoceptor agonist, on the stimulated production of interferon-gamma (IFNgamma), a pro-inflammatory cytokine, and interleukin-10 (IL-10), an immuno-inhibitory cytokine. DESIGN: We measured the in vitro production of IFNgamma and IL-10 by stimulated, diluted whole blood of 16 normal volunteers. The IFNgamma/IL-10 production ratio was computed since this ratio reflects the pro- versus anti-inflammatory capacity of the cultured whole blood. RESULTS: We found that 1) noradrenaline, 10-5 M, 10-6 M, and 10-7 M, significantly suppressed the production of IFNgamma and that noradrenaline, 10-5 M, significantly enhanced the production of IL-10. Clonidine, 10-5 M and 10-7 M, significantly suppressed the production of IFNgamma. Noradrenaline, 10-5 M and 10-6 M, and clonidine, 10-5 M, significantly suppressed the IFNgamma/IL-10 production ratio. There were no significant effects of yohimbine on IFNgamma or IL-10 production. CONCLUSIONS: 1) noradrenaline has significant negative immunoregulatory effects in humans through enhancing the production of IL-10 and suppressing that of IFNgamma; and 2) the suppression of the production of IFNgamma is in part related to alpha2-adrenoceptor activation.