Monguilhott Dalmarco Eduardo, Mendes de Córdova Caio Maurício, Fröde Tânia Silvia
Department of Pharmaceutical Science, Centre of Health Sciences, Regional University of Blumenau, Itoupava Seca, Blumenau, SC, Brazil.
Exp Lung Res. 2011 Sep;37(7):399-407. doi: 10.3109/01902148.2011.570416. Epub 2011 Jul 21.
A promising therapeutic approach to reducing inflammation is to inhibit the production of proinflammatory cytokines (e.g., tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1β], vascular endothelial growth factor alpha (VEGF-α), and, as shown more recently, interleukin-17 [IL-17]). In the present study, the authors have demonstrated the anti-inflammatory effects of mycophenolate mofetil (MMF) in in vivo experiments and have investigated the mechanism of action underlying those effects. Oral administration of MMF significantly inhibited leukocyte influx during the first (4 hours) and second (48 hours) phases of inflammation in a mouse model of pleurisy caused by carrageenan (P < .01). As expected, MMF suppressed protein levels of TNF-α, IL-1β, VEGF-α, and IL-17A (P < .01). This inhibitory effect was due to down-regulation of mRNA expression for these proinflammatory cytokines (P < .01). These results provide evidence of MMF-mediated inhibition of proinflammatory cytokines, and these anti-inflammatory effects are assumed to result mainly from the inhibition of the synthesis and release of TNF-α, IL-1β, VEGF-α, and IL-17A from activated leukocytes. These findings suggest that MMF might be an applicable therapeutic in the regulation of the inflammatory response-a response in which the humoral system plays a pivotal role.
一种很有前景的减轻炎症的治疗方法是抑制促炎细胞因子的产生（例如，肿瘤坏死因子α [TNF-α]、白细胞介素1β [IL-1β]、血管内皮生长因子α [VEGF-α]，以及最近发现的白细胞介素-17 [IL-17]）。在本研究中，作者在体内实验中证明了霉酚酸酯（MMF）的抗炎作用，并研究了这些作用背后的作用机制。在角叉菜胶引起的小鼠胸膜炎模型中，口服MMF在炎症的第一阶段（4小时）和第二阶段（48小时）显著抑制白细胞流入（P <.01）。正如预期的那样，MMF抑制了TNF-α、IL-1β、VEGF-α和IL-17A的蛋白水平（P <.01）。这种抑制作用是由于这些促炎细胞因子的mRNA表达下调（P <.01）。这些结果提供了MMF介导的促炎细胞因子抑制的证据，并且这些抗炎作用被认为主要是由于抑制了活化白细胞中TNF-α、IL-1β、VEGF-α和IL-17A的合成和释放。这些发现表明，MMF可能是调节炎症反应的一种适用疗法——在这种反应中，体液系统起着关键作用。
