The immunosuppressive effects of ciprofloxacin during human mixed lymphocyte reaction.
Interleukin (IL)-18, which is elevated in the plasma during acute rejection after organ transplantation, is known to induce the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40 and CD40 ligand (CD40L) on monocytes, the production of interferon (IFN)-gamma and IL-12 and the proliferation of lymphocytes during the human mixed lymphocyte reaction (MLR). Ciprofloxacin (CIP), which is useful for the clinical treatment of infections due to its antibacterial properties after transplantation, was shown to suppress the IFN-gamma and IL-12 production, the lymphocyte proliferation and the ICAM-1, B7.1, B7.2 and CD40 expression on monocytes during MLR in the presence of IL-18. CIP also induced the production of prostaglandin (PG) E2. In order to determine whether the effects of CIP on the expression of the activation markers were due to CIP-dependent production of PGE2, we examined the effect of cyclooxygenase (COX)-2 and protein kinase A (PKA) inhibitors on the actions of CIP. Thereby, the inhibitors were found to abolish the actions of CIP. These results therefore suggest that CIP might exert its immune modulatory effects via the production of PGE2.
Katsuno
Goutarou
G
Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Takahashi
Hideo Kohka
HK
Iwagaki
Hiromi
H
Mizuno
Kenji
K
Yagi
Takahito
T
Mori
Shuji
S
Saito
Shinya
S
Yoshino
Tadashi
T
Nishibori
Masahiro
M
Tanaka
Noriaki
N
D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002939:Ciprofloxacin / Q000494:pharmacology*; D018920:Coculture Techniques; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009578:Nitrobenzenes / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D016861:Cyclooxygenase Inhibitors; D007166:Immunosuppressive Agents; D020382:Interleukin-18; D007546:Isoquinolines; D009578:Nitrobenzenes; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand; D018664:Interleukin-12; D002939:Ciprofloxacin; D007371:Interferon-gamma; D015232:Dinoprostone; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D007213:Indomethacin