Neutrophil elastase inhibitor (sivelestat) preserves antitumor immunity and reduces the inflammatory mediators associated with major surgery

Surg Today. 2007;37(5):359-65. doi: 10.1007/s00595-006-3409-0. Epub 2007 Apr 30.

Abstract

Purpose: To examine the effects of the administration of perioperative sivelestat, a selective neutrophil elastase inhibitor, on tumor immunity and inflammatory mediators in patients who undergo major surgery.

Methods: Thirteen patients admitted to the hospital for elective surgery were equally randomized into one of two groups: the Sivelestat group (n = 6) and the control group (n = 7). Thereafter, the immunosuppressive acidic protein (IAP), serum interleukin-6 (IL-6), and type 1/type 2 T-helper cell balance were all assessed at several time points before and after surgical intervention.

Results: The serum IL-6 values at 1 and 12 h after surgery and on postoperative days 1 and 3 were all significantly lower in the sivelestat group than in the control group. The IAP values at postoperative days 7 and 28 in the sivelestat group were also significantly lower than those in the control group. There was a significant correlation between the IL-6 level at 1 h after surgery and the IAP level at postoperative days 7 and 28.

Conclusions: In this preliminary study, the perioperative administration of sivelestat was thus suggested to reduce surgical stress by decreasing the cytokine release and preserving the antitumor immunity.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / surgery
  • Digestive System Neoplasms / immunology*
  • Digestive System Neoplasms / surgery*
  • Digestive System Surgical Procedures*
  • Esophageal Neoplasms / immunology
  • Esophageal Neoplasms / surgery
  • Esophagectomy
  • Female
  • Glycine / analogs & derivatives*
  • Glycine / therapeutic use
  • Humans
  • Interleukin-6 / blood*
  • Leukocyte Elastase / antagonists & inhibitors*
  • Liver Neoplasms / immunology
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Pancreaticoduodenectomy
  • Postoperative Period
  • Prospective Studies
  • Serine Proteinase Inhibitors / therapeutic use
  • Single-Blind Method
  • Stress, Physiological / immunology*
  • Sulfonamides / therapeutic use*
  • Th1 Cells / metabolism
  • Th2 Cells / metabolism

Substances

  • Interleukin-6
  • Serine Proteinase Inhibitors
  • Sulfonamides
  • sivelestat
  • Leukocyte Elastase
  • Glycine