Interleukin-10 attenuates proinflammatory cytokine production and improves survival in lethal pancreatitis

Am Surg. 2001 Mar;67(3):237-41; discussion 241-2.

Abstract

Given that interleukin (IL)-10 (IL-10) serves as a potent down-regulator of specific proinflammatory cytokines we reasoned that its administration should improve outcome in situations in which the biological response to a severe inflammatory challenge is the critical determinant of survival. To test our hypothesis we administered IL-10 in the setting of lethal pancreatitis to determine its effect on proinflammatory cytokine production and survival. We divided Sprague-Dawley rats into three groups. Controls (Group 1, n = 5) received a sham laparotomy. We induced pancreatitis in Group 2 (n = 9) and Group 3 (n = 9) via laparotomy and intrapancreatic infiltration of one mL of 5 per cent sodium taurocholate. Group 2 was treated only with saline, whereas Group 3 was treated with 10,000 units of IL-10 (in saline) at 30 minutes, 3.5 hours, and 6.5 hours after induction of pancreatitis. Serial blood samples were obtained at 6.5 hours for measurement of amylase, IL-1, and IL-6. The Kaplan-Meier method, Wilcoxon test, and Student's t test were used for analysis. Seven-day survival was 100, 0, and 45 per cent in Groups 1, 2, and 3, respectively. Production of amylase, IL-1, and IL-6 was lower in the IL-10-treated group (Group 3) compared with the group treated with saline alone (Group 2, P < 0.05). We conclude that administration of IL-10 in the setting of otherwise 100 per cent lethal experimental pancreatitis significantly reduces production of amylase, IL-1, and IL-6 and improves survival.

MeSH terms

  • Amylases / blood
  • Animals
  • Biomarkers / blood
  • Cytokines / drug effects*
  • Disease Models, Animal*
  • Drug Evaluation, Preclinical
  • Humans
  • Interleukin-1 / blood
  • Interleukin-10 / blood
  • Interleukin-10 / immunology
  • Interleukin-10 / therapeutic use*
  • Interleukin-6 / blood
  • Life Tables
  • Male
  • Pancreatitis / chemically induced
  • Pancreatitis / immunology
  • Pancreatitis / metabolism
  • Pancreatitis / mortality
  • Pancreatitis / therapy*
  • Proportional Hazards Models
  • Rats
  • Rats, Sprague-Dawley
  • Statistics, Nonparametric
  • Survival Analysis
  • Taurocholic Acid

Substances

  • Biomarkers
  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • Interleukin-10
  • Taurocholic Acid
  • Amylases