Macrolide antibiotics such as erythromycin have been reported to be effective for asthma. However, the precise mechanisms of this effect remain unclear. We studied the effect of erythromycin, clarithromycin, josamycin, and other antibiotics on the release by eosinophils of interleukin-8 (IL-8), a potent chemokine for inflammatory cells, including eosinophils themselves. Human eosinophils were isolated from atopic patients, and the effects of the drugs on IL-8 release were evaluated. Only 14-member macrolides (erythromycin and clarithromycin) showed a concentration-dependent suppressive effect on IL-8 release (control, 100%; erythromycin at 1 microgram/ml, 67.82% +/- 3.45% [P < 0.01]; clarithromycin at 5 micrograms/ml, 56.81% +/- 9.61% [P < 0.01]). The effect was found at therapeutic concentrations and appeared to occur at the posttranscriprtional level. In contrast, a 16-member macrolide (josamycin) had no significant effect. We suggest that 14-member macrolides inhibit IL-8 release by eosinophils and may thereby prevent the autocrine cycle necessary for the recruitment of these cells into the airways.