The results of a study on the interaction of cytokines with beta-adrenergic receptors (betaAR) in cultured human lung tumor cells indicate that the density of betaAR, assayed by (125)I-pindolol binding, is increased 2-3-fold by a 24 hr incubation of A549 cells with IL-1alpha, IL-1beta, and TNFalpha (EC50:: 2.7, 8.2 and 24 pM, respectively), while a series of other cytokines do not have this effect. Cortisol also increased betaAR density (EC50: 30 nM), and markedly potentiated the effects of IL-1alpha, IL-1beta, and TNFalpha. Neither IL-1 nor cortisol influenced the proportion of cell surface vs. internalized betaAR. The IL-1-induced increase in betaAR density was half-maximal after 6 hr., was reversible at a similar rate, and was blocked by 1 (mu)M of cycloheximide. The effect of IL-1 on betaAR was specific, as the density of glucocorticoid receptors, measured by 3H-dexamethasone binding, was reduced by IL-1. Both cortisol and IL-1 potentiated the isoproterenol-induced increase in cAMP accumulation. IL-1 inhibited cell proliferation and thymidine uptake, and increased the adherence of A549 cells to the plastic culture flask, as quantified by a cell detachment assay. The effect of IL-1 on cell adherence was not inhibited by cycloheximide. Cortisol decreased cell adherence and prevented the IL-1-induced increase in adherence. The results indicate that multiple effects of IL-1 in a cultured tumor cell line involve different mechanisms, suggesting heterogeneity of IL-1 receptors or coupling of the IL-1 receptor to distinct, nuclear and nonnuclear, effector pathways. Earlier studies indicated that IL-1 selectively upregulated the beta2AR subtype. Ongoing experiments are aimed to determine the effects of IL-1 at the level of the transcription of the beta2AR and beta1AR genes.
