TY - JOUR T1 - Effect of Itraconazoles on the Production of Pro-inflammatory Substances in Mouse Macrophage-like Cells JF - In Vivo JO - In Vivo SP - 709 LP - 713 VL - 24 IS - 5 AU - TAKAO KATO AU - NORIO HORIE AU - KEN HASHIMOTO AU - KAZUE SATOH AU - TETSUO SHIMOYAMA AU - TADAYOSHI KANEKO AU - KAORU KUSAMA AU - HIROSHI SAKAGAMI Y1 - 2010/09/01 UR - http://iv.iiarjournals.org/content/24/5/709.abstract N2 - Background, Materials and Methods: Synthetic triazoles are widely used for the treatment of fungal infection. In order to understand their possible anti-inflammatory action, we investigated the effect of itraconazole and its hydroxylated derivative (hydroxyitraconazole) on the production of various pro-inflammatory substances by mouse macrophage-like RAW264.7 cells. Results: These compounds did not apparently show any growth inhibitory or stimulatory effects over a wide range of concentrations (0.2-50 μg/ml). Itraconazoles dose-dependently increased the production of prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α) without affecting the production of interleukin-1β (IL-1β) and nitric oxide (NO). LPS treatment significantly enhanced the production of NO, PGE2, TNF-α and IL-1β. The addition of itraconazoles to LPS-stimulated RAW264.7 cells significantly reduced the production of NO, but rather enhanced the production of PGE2, TNF-α and IL-1β. ESR spectroscopy demonstrated that itraconazoles did not significantly scavenge NO and superoxide anion radicals, indicating that the inhibition of NO production by itraconazoles is not due to their radical-scavenging activity. Hydroxyitraconazole was slightly more cytostatic, and more efficiently inhibited NO production, but enhanced the production of other pro-inflammatory substances. Conclusion: These data suggest that itraconazoles regulate NO and other pro-inflammatory substances differently in activated macrophages. ER -