Effects of long-term administration of erythromycin on cytokine production in rat alveolar macrophages.

Low-dose long-term erythromycin treatment has recently been reported to be very effective in patients with chronic respiratory infection and inflammation. This effect of erythromycin was thought to be not antibacterial but anti-inflammatory. However, the exact mechanism of the effect of erythromycin has not yet been clarified. The aims of this study were to investigate the effects of erythromycin on cytokine production and its mechanisms of actions in rat alveolar macrophages. Using rats with or without administration of erythromycin for 3 months, the production of the cytokines tumour necrosis factor-or (TNF-alpha), cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2alpha by enzyme-linked immunosorbent assay and the expression of TNF-alpha and CINC-1 messenger ribonucleic acid (mRNA) by Northern blotting in rat alveolar macrophages were analysed. CINC-1 is the rat counterpart of human interleukin-8, and CINC-2alpha of human macrophage inflammatory peptide-2. Erythromycin reduced cytokine production and secretion when cytokines was induced by lipopolysaccharide treatment. Conversely, erythromycin slightly upregulated the expression of cytokine mRNA. These results suggest that erythromycin inhibits cytokine production and exhibits anti-inflammatory effects by means of a translational and/or posttranslational mechanism.