Division of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Int Immunopharmacol. 2010 May;10(5):580-3. doi: 10.1016/j.intimp.2010.02.005. Epub 2010 Feb 13.
The pathogenesis of sepsis is mediated in part by bacterial endotoxin, which stimulates macrophages/monocytes to sequentially release proinflammatory factors like TNF-alpha and IL-1beta. Fluorofenidone (AKF-PD) is a novel pyridone agent, which exerts a strong antifibrotic effect. In this work, we showed that AKF-PD also exert an inhibitory effect on acute systemic inflammatory response. AKF-PD treatment significantly increased survival in animals with established endotoxemia. In addition, AKF-PD treatment significantly reduced circulating levels of TNF-alpha and IL-1beta during endotoxemia. In macrophage cultures, AKF-PD inhibited the release of TNF-alpha and IL-1beta in a dose-dependent manner. In conclusion, these results indicate that AKF-PD inhibits the release of the proinflammatory cytokines (TNF-a and IL-1beta) and improves survival during lethal endotoxemia, which suggest this new pyridone agent can be a novel candidate for therapy of septic shock.
脓毒症的发病机制部分是由细菌内毒素介导的，细菌内毒素刺激巨噬细胞/单核细胞依次释放 TNF-α和 IL-1β等促炎因子。氟非尼酮（AKF-PD）是一种新型吡啶酮类药物，具有很强的抗纤维化作用。在这项工作中，我们表明 AKF-PD 还对急性全身炎症反应具有抑制作用。AKF-PD 治疗可显著提高内毒素血症动物的存活率。此外，AKF-PD 治疗可显著降低内毒素血症期间循环 TNF-α和 IL-1β的水平。在巨噬细胞培养物中，AKF-PD 以剂量依赖性方式抑制 TNF-α和 IL-1β的释放。总之，这些结果表明 AKF-PD 可抑制促炎细胞因子（TNF-α和 IL-1β）的释放，并可改善致死性内毒素血症期间的存活率，这表明这种新型吡啶酮类药物可能成为治疗感染性休克的新型候选药物。
