Enhancement of interleukin 2 production by quinolone-treated human mononuclear leukocytes.
Previous studies have shown that lectin-induced human mononuclear leukocyte (MNL) proliferation was influenced by quinoline derivative antibiotics (quinolones), depending on both the dose and the antimicrobial agent used. Since the production of interleukin-2 (IL-2) is known to be involved in the proliferation of immune cells, we investigated the effects of three quinolones: ciprofloxacin (Cip), ofloxacin (Ofl) and pefloxacin (Pef) on IL-2 production in vitro by phytohemagglutinin (PHA)-stimulated human MNL. IL-2 activity in the supernatants of PHA-stimulated MNL was found to be enhanced by quinolones in a dose- and time-dependent manner. Increased IL-2 activity was observed using Cip, Ofl or Pef at therapeutically achievable blood concentrations (5-10 micrograms/ml). Since at these concentrations the PHA-induced proliferative response of MNL was not impaired by quinolones, the increased recovered IL-2 activity was not related to a decreased absorption of IL-2 by activated MNL. At high antibiotic concentrations (25 micrograms/ml), the enhanced IL-2 activity might be related (i) to increased accumulation resulting from the decreased proliferation induced by the quinolones at these concentrations, and (ii) to a true increased IL-2 production by the cells. In fact, an increased IL-2 recovery in presence of quinolones was always observed after blocking the cell cycle by mitomycin C, and was therefore independent of DNA-synthesis. Furthermore, the expression of IL-2 receptors was not modified by Cip, Ofl or Pef. These data show that quinolones increased IL-2 synthesis by MNL and suggest the potential usefulness of these antibiotics, not only as antimicrobial agents, but also as modulators of immune responses.
D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008213:Lymphocyte Activation; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D009643:Norfloxacin / Q000031:analogs & derivatives / Q000494:pharmacology; D015242:Ofloxacin; D010078:Oxazines / Q000494:pharmacology; D015366:Pefloxacin; D011804:Quinolines / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism; D015375:Receptors, Interleukin-2
D000890:Anti-Infective Agents; D007376:Interleukin-2; D008937:Mitomycins; D010078:Oxazines; D011804:Quinolines; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D015366:Pefloxacin; D016685:Mitomycin; D002939:Ciprofloxacin; D015242:Ofloxacin; D009643:Norfloxacin