Tumor necrosis factor produces homologous desensitization of lymphocyte β₂-adrenergic responses

The effect of tumor necrosis factor α (TNFα) on lymphocyte β₂- adrenergic receptor response is reported. Isoproterenol-mediated cyclic-3,5- adenosine monophosphate (cAMP) production by intact lymphocytes preincubated with isotonic buffer or TNFα was studied TNFα at 1 ng/ml and 100 ng/ml reduced isoproterenol-stimulated cAMP generation by 15% and 27% over the respective basal values. Stimulation of lymphocytes with forskolin or prostaglandin E₁ was minimally affected, indicating that the effect of TNFα was due neither to nonspecific toxicity nor to its influence on the nucleotide regulatory protein complex or the catalytic adenylate cyclase component of the β₂-adrenergic receptor complex system. Rather, TNFα appeared to affect the receptor recognition unit specifically. TNFα causes homologous desensitization of lymphocyte β₂-adrenergic receptor response.