Immunomodulatory activities of fluoroquinolones.
A review of published data on the in vitro, ex vivo, in vivo and clinical effects of fluoroquinolones on the synthesis of cytokines is provided. Fluoroquinolones (FQs) were found to affect both cellular and humoral immunity. In general, FQs exert their modulating effects only when used together with a co-stimulant. The in vitro studies generated heterogeneous data because of inhomogeneous effects triggered by different types of co-stimulants and differing responses of various cell lines on the stimuli. However, there is the general trend that FQs decrease the synthesis of pro-inflammatory cytokines. Studies in experimental animals generated homogenous data. All the FQs studied exerted significant clinical effects by attenuating cytokine responses in vivo. The FQs were found to be effective in vivo either in infections caused by organisms against which these are inactive or when dosed suboptimally, so that serum levels were lower than the susceptibilities of the causative pathogens. These in vivo effects were correlated with a significant decrease in pro-inflammatory cytokines like Il-1 and TNF. In addition, FQs were found to upregulate hematopoiesis. These immunomodulatory effects can be attributed in particular to those FQs with a cyclopropyl-moiety at the position N1 of the quinolone core structure, i. e. ciprofloxacin, moxifloxacin, grepafloxacin, sparfloxacin. The immunomodulatory effects of the FQs are due to their effects on intracellular cyclic AMP and phosphodiesterases, on transcription factors such as NF-kappa B, activator protein 1 and a triggering effect on the eucaryotic equivalent of bacterial SOS response. All these studies indicate that FQs exert immunomodulatory activities in particular in latent or chronic infections.
Dalhoff
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Institute for Infection Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Brunswiker Str. 4, 24105 Kiel, Germany. ADalhoff@t-online.de
D000818:Animals; D000900:Anti-Bacterial Agents / Q000276:immunology* / Q000494:pharmacology*; D016207:Cytokines / Q000276:immunology; D024841:Fluoroquinolones / Q000276:immunology* / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007109:Immunity / Q000187:drug effects* / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects
D000900:Anti-Bacterial Agents; D016207:Cytokines; D024841:Fluoroquinolones