Fourteen-member macrolides inhibit interleukin-8 release by human eosinophils from atopic donors

Macrolide antibiotics such as erythromycin have been reported to be effecti ve for asthma, However, the precise mechanisms of this effect remain unclea r, We studied the effect of erythromycin, clarithromycin, josamycin, and ot her antibiotics on the release by eosinophils of interleukin-8 (IL-8), a po tent chemokine for inflammatory cells, including eosinophils themselves. Hu man eosinophils were isolated from atopic patients, and the effects of the drugs on IL-8 release were evaluated, Only 14-member macrolides (erythromyc in and clarithromycin) showed a concentration-dependent suppressive effect on IL-8 release (control, 100%; erythromycin at 1 mu g/ml, 67.82% +/- 3.45% [P < 0.01]; clarithromycin at 5 mu g/ml, 56.81% +/- 9.61% [P < 0.01]), The effect was found at therapeutic concentrations and appeared to occur at th e posttranscriprtional level. In contrast, a 16-member macrolide (josamycin ) had no significant effect, We suggest that 14-member macrolides inhibit I L-8 release by eosinophils and may thereby prevent the autocrine cycle nece ssary for the recruitment of these cells into the airways.