An immunopharmacological analysis of adrenaline-induced suppression of human natural killer cell cytotoxicity.
The circulating catecholamine adrenaline effectively suppressed human natural killer cell cytotoxicity (NKCC) when added to mixtures of effector lymphocytes and 51Cr-labelled target cells in a 4-hour 51Cr release assay in vitro. The effect was mimicked by the beta 2-receptor agonist terbutaline but not by the beta 1-receptor agonist prenalterol or the alpha 1/alpha 2-receptor agonist clonidine. Adrenaline-induced NKCC suppression was completely and potently antagonized by the mixed beta 1/beta 2-receptor antagonist propranolol and the selective beta 2-receptor antagonist ICI 118,551 but not by the beta 1-selective antagonist metoprolol. By comparing the adrenaline sensitivity of high-density (HD) and low-density (LD) lymphocytes, fractionated by Percoll density gradient centrifugation, we found that HD cells appeared more sensitive to adrenaline-induced suppression than LD cells. In both types of effector cells, adrenaline significantly suppressed NKCC at a final concentration of 10(-11) M. Pretreatment of LD effector cells with IFN-alpha reduced the NKCC suppression by subsequent adrenaline treatment. Pretreatment with recombinant IL-2 virtually abolished the response to adrenaline. This effect was noted also when IL-2 and adrenaline were incubated simultaneously during the 4-hour 51Cr release assay. Our data suggest a role for adrenaline, via lymphocyte beta 2-receptor activation, in the regulation of natural killer cells.
Hellstrand
K
K
Department of Clinical Virology, University of Göteborg, Sweden.
Hermodsson
S
S
D000318:Adrenergic beta-Agonists / Q000145:classification / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004306:Dose-Response Relationship, Immunologic; D004837:Epinephrine / Q000494:pharmacology*; D005312:Fetal Blood / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007372:Interferons / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000502:physiology
D000318:Adrenergic beta-Agonists; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011943:Receptors, Adrenergic, beta; D007372:Interferons; D004837:Epinephrine