Effect of ciprofloxacin-induced prostaglandin E2 on interleukin-18-treated monocytes

Hideo Kohka Takahashi, Hiromi Iwagaki, Dong Xue, Goutarou Katsuno, Sachi Sugita, Kenji Mizuno, Shuji Mori, Shinya Saito, Tadashi Yoshino, Noriaki Tanaka, Masahiro Nishibori

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Ciprofloxacin, a fluorinated 4-quinolone, is useful for the clinical treatment of infections due to its antibacterial properties and also modulates the immune response of monocytes isolated from human peripheral blood mononuclear cells. In the present study, we found that ciprofloxacin induced the production of prostaglandin E2 in monocytes in a concentration-dependent manner regardless of the presence of interleukin-18 by enhancing the expression of cyclooxygenase-2 protein and that this in turn led to the elevation of intercellular cyclic AMP in monocytes via the stimulation of prostaglandin receptors. The prostaglandin E2 and cyclic AMP production increased by ciprofloxacin was inhibited by indomethacin, a nonselective cyclooxygenase-2 inhibitor, and NS398, a selective cyclooxygenase-2 inhibitor. In addition, ciprofloxacin suppressed the interleukin-18-induced production of tumor necrosis factor alpha, gamma interferon, and interleukin-12 in peripheral blood mononuclear cells by inhibiting the expression of intercellular adhesion molecule 1, B7.1, B7.2, and CD40 on monocytes, and this effect could be reversed by the addition of indomethacin or NS398. These results indicate that ciprofloxacin exerts immunomodulatory activity via the production of prostaglandin E2 and imply therapeutic potential of ciprofloxacin for the treatment of systemic inflammatory responses initiated by interleukin-18.

Original languageEnglish
Pages (from-to)3228-3233
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume49
Issue number8
DOIs
Publication statusPublished - Aug 2005

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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