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-1 alpha and IL-1 beta synthesis, each species was measured in the supernatants and cell lysates of monocyte cultures over a 4-day period using IL-1 alpha and IL-1 beta-specific ELISA methods. Cip had a post-transcriptional differential effect on the production of IL-1 alpha and IL-1 beta, reducing the total amount of IL-1 beta produced by LPS-stimulated monocytes, while that of IL-1 alpha 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 cell-associated activity. Cip is, to our knowledge, the first pharmacological agent found to have a differential effect on the synthesis of IL-1 alpha and IL-1 beta. It may form the basis for new pharmacological agents capable of selectively reducing the systemic effects of IL-1 without affecting local activity.
Bailly
S
S
INSERM U. 294, Laboratoire d'Immunologie et d'Hématologie, Chu X. Bichat, Paris, France.
Mahe
Y
Y
Ferrua
B
B
Fay
M
M
Tursz
T
T
Wakasugi
H
H
Gougerot-Pocidalo
M A
MA
D015152:Blotting, Northern; D002939:Ciprofloxacin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D015363:Quinolones / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors
D007375:Interleukin-1; D008070:Lipopolysaccharides; D015363:Quinolones; D012333:RNA, Messenger; D002939:Ciprofloxacin