QUINOLONE-INDUCED DIFFERENTIAL MODIFICATION OF IL-1-ALPHA AND IL-1-BETA PRODUCTION BY LPS-STIMULATED HUMAN MONOCYTES

We previously reported that ciprofloxacin (Cip), a quinoline-derivative antibiotic, decreases the biological activity of IL-1 released by LPS-stimulated monocytes after 24 hr of culture without affecting cell-associated IL-1 activity. To analyze further the effects of Cip on LPS-induced IL-1α and IL-1β synthesis, each species was measured in the supernatants and cell lysates of monocyte cultures over a 4-day period using IL-1α and IL-1β-specific ELISA methods. Cip had a post-transcriptional differential effect on the production of IL-1α and IL-1β, reducing the total amount of IL-1β produced by LPS-stimulated monocytes, while that of IL-1α was unaffected. In addition, the production of both species was delayed. These findings explain the discrepancy between the Cip-induced alteration of extracellular IL-1 activity and the preservation of cellassociated activity. Cip is, to our knowledge, the first pharmacological agent found to have a differential effect on the synthesis of IL-1α and IL-1β. It may form the basis for new pharmacological agents capable of selectively reducing the systemic effects of IL-1 without affecting local activity. © 1990.