Modulation of interleukin-1 and tumor necrosis factor expression by β-adrenergic agonists in mouse ameboid microglial cells

Brain macrophages (ameboid microglial cells) purified to homogeneity and cultured in vitro synthesize and release IL-1 and TNF upon stimulation with lipo-polysaccharide (LPS). This induction can be measured at the levels of transcription and translation. In the present study we have analysed whether certain compounds normally present in the nervous tissue could regulate cytokine production by brain macrophages. We demonstrate that the β-adrenergic agonist isoproterenol, at a concentration of 10-7 M; inhibits the LPS-induced transcription and release of TNFα. At the same concentration, isoproterenol increases the accumulation of IL-1α and IL-1β mRNAs. In spite of its strong effect on IL-1 mRNA accumulation, the adrenergic agonist did not enhance IL-1 activity produced by microglial cells. On the contrary, as is the case for TNF, the LPS-induced production of IL-1 was inhibited by isoproterenol. The effects of isoproterenol on cytokine production specifically involve the β2 and not the β1 adrenergic receptor. It thus appears (i) that the accumulation of mRNAs coding for TNFα on one hand and IL-1α and β on the other is regulated in two opposite ways by the stimulation of the β2-adrenergic receptor and (ii) that mRNA accumulation and cytokine production and secretion are not necessarily coupled.