Immunomodulating Activity of Quinolones: Review

Fluorinated quinolones exert their bactericidal activity by inhibiting bacterial type II topoisomerases. At therapeutic concentrations, quinolones superinduce interleukin-2 (IL-2) and interferon-gamma production by mitogen-activated human peripheral blood T lymphocytes. At the molecular level, a stronger activation of the nuclear factor AP-1 ('activator protein-1') is observed in cells incubated with ciprofloxacin, resulting in enhanced cytokine gene transcription. Several cytokine and immediate early (e.g., c-fos and c-jun) mRNAs are upregulated by ciprofloxacin, possibly reflecting a mammalian stress response. In cultures with murine splenocytes, quinolones enhance IL-3 and granulocyte-macrophage colony stimulating factor (GM-CSF) synthesis. The stimulation of these hematopoietic growth factors prolongs survival of mice with depressed bone marrow and prevents experimental antiphospholipid syndrome (APS). In contrast, quinolones inhibit both human and mouse monocytic IL-1 and TNF-alpha synthesis, an effect that is beneficial in rat experimental type II collagen induced arthritis and LPS-induced septic chock in mice. The intriguing immunomodulatory activities of fluoroquinolones warrant future investigations with new tailored derivatives.