Interleukin-10 attenuates proinflammatory cytokine production and improves survival 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 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.
Department of Surgery, Washington Hospital Center, DC 20010-2975, USA.
J W
JW
Cook
S
S
Karakozis
D
D
Kim
H
H
Provido
E
E
Gongora
J R
JR
Kirkpatrick
D000681:Amylases / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000187:drug effects*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D015993:Life Tables; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D016016:Proportional Hazards Models; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013656:Taurocholic Acid
D015415:Biomarkers; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016753:Interleukin-10; D013656:Taurocholic Acid; D000681:Amylases