Effect of Clarithromycin on Endogenous Glucocorticoid Levels in Mice

The efficacy of erythromycin (EM) and clarithromycin (CAM) is well documented for the management of chronic inflammatory respiratory tract disease. However, the precise mechanism of action of these drugs is still controversial. We previously reported that EM increased serum glucocorticoid (GC) levels and suggested that this increase may be a mechanism of action of the drug. To investigate whether other macrolides had similar activity, we studied the effect of a new macrolide, CAM, on serum GC levels in mice. Intraperitoneal injections of CAM increased the serum GC levels in a dose-dependent manner, with the increase completely suppressed by pretreatment with dexamethasone. These results suggest that CAM increases serum GC levels through activation of the hypothalamo-pituitary adrenocortical axis, and that the antiinflammatory activity of CAM appears to exert its influence via an increase in serum GC levels.