Effect of ciprofloxacin-induced prostaglandin E2 on interleukin-18-treated monocytes.
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 E(2) 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 E(2) 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 E(2) and imply therapeutic potential of ciprofloxacin for the treatment of systemic inflammatory responses initiated by interleukin-18.
Takahashi
Hideo Kohka
HK
Department of Pharmacology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. mbori@md.okayama-u.ac.jp
Iwagaki
Hiromi
H
Xue
Dong
D
Katsuno
Goutarou
G
Sugita
Sachi
S
Mizuno
Kenji
K
Mori
Shuji
S
Saito
Shinya
S
Yoshino
Tadashi
T
Tanaka
Noriaki
N
Nishibori
Masahiro
M
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002939:Ciprofloxacin / Q000494:pharmacology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D020382:Interleukin-18 / Q000276:immunology / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D015815:Cell Adhesion Molecules; D016207:Cytokines; D020382:Interleukin-18; D008565:Membrane Proteins; D002939:Ciprofloxacin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin