Roflumilast reverses polymicrobial sepsis-induced liver damage by inhibiting inflammation in mice

摘要: Sepsis is a life-threatening syndrome accompanied by an overwhelming inflammatory response and organ dysfunction. Selective targeting of phosphodiesterase 4 (PDE4) currently being investigated as effective therapeutic approach for inflammation-associated diseases. Roflumilast selective PDE4 inhibitor, used the treatment severe chronic obstructive pulmonary disease in clinic. However, its role sepsis-induced liver damage remains unclear. In present study, we evaluated effects roflumilast mice with cecal ligation puncture-induced sepsis, underlying mechanism. We found that improved survival septic reducing bacterial load locally systemically, inhibiting expression pro-inflammatory cytokines interleukin-6 tumor necrosis factor alpha, alleviating injury. These were associated inhibition nuclear translocation factor-kappa B (NF-κB), well degradation NF-κB inhibitory protein alpha. The phosphorylation p38 mitogen-activated kinase (MAPK) was also markedly inhibited roflumilast. Moreover, significantly suppressed activation signal transducer activator transcription 3 (STAT3) upstream Janus 1 2. Taken together, these results indicate prevents polymicrobial sepsis likely suppressing NF-κB, MAPK, STAT3 pathways.