TUMOR-NECROSIS-FACTOR PRODUCES HOMOLOGOUS DESENSITIZATION OF LYMPHOCYTE BETA-2-ADRENERGIC RESPONSES

The effect of tumor necrosis factor alpha (TNFalpha) on lymphocyte bet a2-adrenergic receptor response is reported. Isoproterenol-mediated cy clic-3,5-adenosine monophosphate (cAMP) production by intact lymphocyt es preincubated with isotonic buffer or TNFalpha was studied. TNFalpha at 1 ng/ml and 100 ng/ml reduced isoproterenol-stimulated cAMP genera tion by 15% and 27% over the respective basal values. Stimulation of l ymphocytes with forskolin or prostaglandin E1 was minimally affected, indicating that the effect of TNFalpha was due neither to nonspecific toxicity nor to its influence on the nucleotide regulatory protein com plex or the catalytic adenylate cyclase component of the beta2-adrener gic receptor complex system. Rather, TNFalpha appeared to affect the r eceptor recognition unit specifically. TNFalpha causes homologous dese nsitization of lymphocyte beta2-adrenergic receptor response.