INTERLEUKIN-10 PREVENTS DEATH IN LETHAL NECROTIZING PANCREATITIS IN MICE

Background, Cytokines derived from macrophages may play an integral ro le in the evolution of acute pancreatitis. Interleukin-10 (IL-10), a p otent antiinflammatory cytokine, prevents the activation of macrophage s and their release of inflammatory cytokines. The aim of this study w as to determine whether treatment with IL-10 decreased the severity of experimental acute pancreatitis. Methods, Thirty female Swiss Webster mice were divided into three groups. Acute pancreatitis was induced b y using a choline-deficient, 0.5% ethionine supplemented (CDE) diet. G roup A (controls) received CDE diet alone. Group B was pretreated with 10,000 units of intraperitoneal IL-10 at the onset of feeding and eve ry 8 hours thereafter. Group C received IL-10 33 hours after beginning the CDE diet and every 8 hours thereafter. One half of the animals in each group was killed at 54 hours; the remaining living animals were killed at 80 hours, Serum amylase levels (units per liter) were determ ined at 54 and 80 hours. Pancreata were harvested and fixed in formali n. Histologic characteristics were graded on a scale from 0 to 4 (norm al to most abnormal) in a blinded fashion by two investigators. Result s, Serum amylase level and histologic score (edema, inflammation, hemo rrhage, and necrosis) were significantly reduced when IL-10 was admini stered either prophylactically or therapeutically (p < 0.01). At 44 ho urs all animals were alive, Mortality was reduced at 80 hours in both groups treated with IL-10 compared with those fed the CDE diet alone ( p < 0.001), Conclusions, These results suggested that macrophages play an integral role in determining the severity of acute pancreatitis in this animal model. The finding that IL-10 decreased inflammation and prevented death, even when given after acute pancreatitis was establis hed suggests that it may have potential for clinical use.