Regulation of interleukin‐10 production by β‐adrenergic agonists

Publisher Website
Google Scholar
Abstract
Catecholamines have been shown to inhibit some aspects of macrophage activation through a β receptor‐dependent mechanism. This study was undertaken to analyze the effects of isoproterenol, a specific β‐adrenergic agonist, on the synthesis of interleukin‐10 (IL‐10), a major macrophage‐deactivating factor. Isoproterenol increased IL‐10 release from lipopolysaccharide‐(LPS)‐activated mouse peritoneal macrophages in a dose‐dependent manner. A significant effect was already observed with 1 μM isoproterenol, while a 4.5‐fold increase was achieved with 10 μM. This increase was observed only if macrophages were exposed to isoproterenol for at least 2 h before LPS challenge. It was apparent within 0.5 h and persisted through 24 h at all the LPS concentrations used. A similar increase was observed at the IL‐10 mRNA level, as judged by enzyme‐linked immunosorbent assay‐polymerase chain reaction. The macrophage response to isoproterenol that led to cyclic AMP accumulation was markedly inhibited by H‐89, a potent inhibitor of protein kinase A. These data suggest the involvement of cyclic AMP in the regulation of IL‐10 synthesis by isoproterenol. IL‐10 was in turn partly responsible for a reduction in tumor necrosis factor‐α synthesis. In vivo, the administration of oxprenolol, a β‐receptor antagonist, significantly reduced serum IL‐10 levels 90 min after LPS challenge. Thus, the present study provides the first evidence that endogenous catecholamines are of critical importance in determining the magnitude of the IL‐10 response in experimental endotoxemia.