Effect of catecholamines on IL-2 production and NK cytotoxicity of rats in vitro

To explore effects of exogenous and endogenous catecholamines on function of lymphocytes and primary mechanisms mediating the effects.

Splenocytes of rats were exposed to norepinephrine (NE), alpha- or beta-adrenoceptor antagonists plus NE, or alpha-methyl-p-tyrosine (alpha-MT), and then concanavalin A (Con A)-induced interleukin-2 (IL-2) production and natural killer (NK) cell cytotoxicity were determined by MTT assay and LDH assay, respectively.

Optical density (OD) values of NE-treated groups, which reflected IL-2 production, were 0.63, 0.61, and 0.60, respectively for 10(-10), 10(-9), and 10(-8) mol/L NE. They were all significantly reduced in comparison with control value of 0.68 (P<0.01). The effect of NE was blocked by either phentolamine (an alpha-adrenoceptor antagonist) or propanolol (a beta-adrenoceptor antagonist). OD values of alpha-MT, an inhibitor of tyrosine hydroxylase, at doses of 10(-10), 10(-9), and 10(-8) mol/L respectively were 0.71, 0.71, and 0.69, which were all notably higher than that of control (0.65, P<0.01). NK cytotoxicity was markedly attenuated by both NE and alpha-MT at the three doses mentioned above (17.69 %, 17.06 %, and 16.89 % versus 25.18 % for NE; 18.85 %, 18.44 %, and 17.04 % versus 23.22 % for alpha-MT; all P<0.01). The suppression of NK cytotoxicity by NE was prevented by propranolol but not by phentolamine.

Exogenous NE exerts a suppressive action in modulating functions of T and NK cells, with the former via both alpha- and beta-adrenoceptor mediated mechanisms and the later mainly through beta-adrenoceptors. Endogenous catecholamines synthesized by lymphocytes have also an autoregulatory effect on the lymphocytes themselves.