Evidence of an anti-inflammatory effect of mycophenolate mofetil in a murine model of pleurisy

Abstract

ABSTRACTA 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.