The neutrophil elastase inhibitor sivelestat suppresses accelerated gastrointestinal tumor growth via peritonitis after cecal ligation and puncture

Background: We examined whether tumor growth is enhanced by cecal ligation and puncture (CLP) and suppressed by a neutrophil elastase inhibitor, sivelestat. Materials and Methods: C57BL/6 mice were divided in CLP/sivelestat, CLP alone, and control (simple laparotomy) groups. Murine CT26 colon carcinoma cells were injected subcutaneously into the back of each mouse and tumor growth and serum cytokine levels were assessed. Results: Mice subjected to CLP alone exhibited enhanced tumor growth compared to controls with subcutaneously injected CT26 cells (0.64±0.24 g vs. 0.021±0.027 g, p<0.001), while treatment with CLP/sivelestat produced smaller tumors than CLP alone (0.28±0.23 g vs. 0.64±0.24 g, p=0.006). Cytokine assays showed suppressed production of interleukin (IL)-6 and IL-10 in the CLP/sivelestat group, and increased IL-6 and IL-10 in the CLP-alone group. Conclusion: Intraabdominal inflammation induced by CLP enhances the growth of subcutaneously implanted tumors, while perioperative administration of sivelestat suppresses tumor growth by affecting systemic inflammation.