Interleukin-10 attenuates proinflammatory cytokine production and improvessurvival in lethal pancreatitis

Given that interleukin (IL)-10 (IL-10) serves as a potent down-regulator of specific proinflammatory cytokines we reasoned that its administration sho uld improve outcome in situations in which the biological response to a sev ere 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 surviva l. 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 mt 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 m inutes, 3.5 hours, and 6.5 hours after induction of pancreatitis. Serial bl ood samples were obtained at 6.5 hours for measurement of amylase, IL-1, an d IL-6. The Kaplan-Meier method, Wilcoxon test, and Student's t test were u sed 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 s aline alone (Group 2, P < 0.05). We conclude that administration of IL-10 i n the setting of otherwise 100 per cent lethal experimental pancreatitis si gnificantly reduces production of amylase, IL-1, and IL-6 and improves surv ival.