Abstract
We described in the last paper how erythromycin given orally enhanced the production of interleukin-1 and tumor necrosis factor by both peripheral blood mononuclear cells and alveolar macrophages. Thus we investigated the kinetics of the immunological action of erythromycin and other macrolides in vitro. When peripheral blood adherent cells from normal volunteers were incubated with erythromycin, clarithromycin or josamycin, the production of interleukin-1α, interleukin-1β and tumor necrosis factor was enhanced dose-dependently. This stimulatory effect depended on the number of cells cultured, and peaked around 8 to 12 h after incubation. These macrolides also had a priming effect, producing interleukin-1α. The production of interleukin-1 was partially blocked by ouabain, H-7 and W-7. We therefore hypothesize that Na+, K+, -ATPase, protein kinase C and/or calmodulin play a role in the stimulatory effect of macrolides.