Interleukin 10 reduces the incidence of pancreatitis after therapeutic endoscopic retrograde cholangiopancreatography.
OBJECTIVE
Prophylactic administration of interleukin (IL)-10 decreases the severity of experimental pancreatitis. Prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in humans is a unique model to study the potential role of IL-10 in this setting.


METHODS
In a single-center, double-blind, randomized, placebo-controlled study, the effect of a single injection of 4 microg/kg (group 1) or 20 microg/kg (group 2) IL-10 was compared with that of placebo (group 0), all administered 30 minutes before therapeutic ERCP. The primary endpoint was the effect of IL-10 on serum levels of amylases and lipases measured 4, 24, and 48 hours after ERCP. The secondary objective was to evaluate changes in plasma cytokines (IL-6, IL-8, tumor necrosis factor) at the same time points and the incidence of acute pancreatitis in the 3 groups. Subjects undergoing a first therapeutic ERCP were eligible for inclusion.


RESULTS
A total of 144 patients were included. Seven were excluded based on intention to treat (n = 1) or per protocol (n = 6). Forty-five, 48, and 44 patients remained in groups 0, 1, and 2, respectively. The 3 groups were comparable for age, sex, underlying disease, indication for treatment, type of treatment, and plasma levels of C-reactive protein (CRP), cytokines, and hydrolases at baseline. No significant difference was observed in CRP, cytokine, and hydrolase plasma levels after ERCP. Forty-three patients developed hyperhydrolasemia (18 in group 0, 14 in group 1, and 11 in group 2; P = 0.297), and 19 patients developed acute clinical pancreatitis (11 in group 0, 5 in group 1, 3 in group 2; P = 0.038). Two severe cases were observed in the placebo group. No mortality related to ERCP was observed. Logistic regression identified 3 independent risk factors for post-therapeutic ERCP pancreatitis: IL-10 administration (odds ratio [OR], 0.46; 95% confidence interval [95% CI], 0.22-0.96; P = 0.039), pancreatic sphincterotomy (OR, 5.04; 95% CI, 1.53-16.61; P = 0.008), and acinarization (OR, 8.19; 95% CI, 1.83-36.57; P = 0.006).


CONCLUSIONS
A single intravenous dose of IL-10, given 30 minutes before the start of the procedure, independently reduces the incidence of post-therapeutic ERCP pancreatitis.
Devière
J
J
Department of Gastroenterology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. jdeviere@ulb.ac.be
Le Moine
O
O
Van Laethem
J L
JL
Eisendrath
P
P
Ghilain
A
A
Severs
N
N
Cohard
M
M
D015746:Abdominal Pain / Q000453:epidemiology; D000208:Acute Disease; D000368:Aged; D000681:Amylases / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002760:Cholangiopancreatography, Endoscopic Retrograde; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015994:Incidence; D007275:Injections, Intravenous; D016753:Interleukin-10 / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008049:Lipase / Q000097:blood; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D011183:Postoperative Complications / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002097:C-Reactive Protein; D008049:Lipase; D000681:Amylases