Immunomodulatory effects of quinolones.
We review data on the in-vitro, ex-vivo, in-vivo, and clinical effects of fluoroquinolones on the synthesis of cytokines and their mechanisms of immunomodulation. In general, most fluoroquinolone derivatives superinduce in-vitro interleukin 2 synthesis but inhibit synthesis of interleukin 1 and tumour necrosis factor (TNF)alpha; furthermore, they enhance significantly the synthesis of colony-stimulating factors (CSF). Fluoroquinolones affect in-vivo cellular and humoral immunity by attenuating cytokine responses. Interleukins 10 and 12 have an important role in the functional differentiation of immunocompetent cells and trigger the initiation of the acquired immune response. In addition, certain fluoroquinolones were seen to enhance haematopoiesis by increasing the concentrations of CSF in the lung as well as in the bone marrow and shaft. Those fluoroquinolones exerting significant effects on haematopoiesis were those with a cyclopropyl moiety at position N1 of their quinolone core structure. Mechanisms that could explain the various immunomodulatory effects of fluoroquinolones include: (1) an effect on intracellular cyclic adenosine-3',5'-monophosphate and phosphodiesterases; (2) an effect on transcription factors such as nuclear factor (NF)kappaB, activator protein 1, NF-interleukin-6 and nuclear factor of activated T cells; and (3) a triggering effect on the eukaryotic equivalent of bacterial SOS response with its ensuing intracellular events. Further studies are required, especially in the clinical setting to exploit fully the potential of the immunomodulatory effect of fluoroquinolones during, for example, immunosuppression, chronic airway inflammatory diseases, and sinusitis.
Dalhoff
Axel
A
Institute for Medical Microbiology and Virology, Universitätsklinikum Schleswig Holstein, Campus Kiel, Germany. axel.dalhoff.ad@bayer-ag.de <axel.dalhoff.ad@bayer-ag.de>
Shalit
Itamar
I
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001372:Aza Compounds; D002939:Ciprofloxacin / Q000494:pharmacology; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D024841:Fluoroquinolones; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D023421:Models, Animal; D000077266:Moxifloxacin; D009287:Naphthyridines / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011804:Quinolines
D000276:Adjuvants, Immunologic; D000890:Anti-Infective Agents; D001372:Aza Compounds; D016207:Cytokines; D024841:Fluoroquinolones; D009287:Naphthyridines; D010879:Piperazines; D011804:Quinolines; D002939:Ciprofloxacin; C080163:trovafloxacin; D015242:Ofloxacin; C075375:grepafloxacin; D000077266:Moxifloxacin