Neutrophil elastase inhibitor (sivelestat) preserves antitumor immunity and reduces the inflammatory mediators associated with major surgery.
OBJECTIVE
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.
Akamoto
Shintaro
S
Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kita, Kagawa 761-0793, Japan.
Okano
Keiichi
K
Sano
Takanori
T
Yachida
Shinichi
S
Izuishi
Kunihiko
K
Usuki
Hisashi
H
Wakabayashi
Hisao
H
Suzuki
Yasuyuki
Y
D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000601:surgery; D004067:Digestive System Neoplasms / Q000276:immunology* / Q000601:surgery*; D013505:Digestive System Surgical Procedures; D004938:Esophageal Neoplasms / Q000276:immunology / Q000601:surgery; D016629:Esophagectomy; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008113:Liver Neoplasms / Q000276:immunology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016577:Pancreaticoduodenectomy; D011184:Postoperative Period; D011446:Prospective Studies; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use; D016037:Single-Blind Method; D013312:Stress, Physiological / Q000276:immunology*; D013449:Sulfonamides / Q000627:therapeutic use*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D015850:Interleukin-6; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine