Original article High plasma levels of the pro-inflammatory cytokine IL-22 and the anti-inflammatory cytokines IL-10 and IL-1ra in acute pancreatitis Philippe Vasseur a, b, * , Iris Devaure a , Jacques Sellier c , Adriana Delwail b , Carine Chagneau-Derrode a , Florian Charier a , David Tougeron a, b , Jean-Pierre Tasu c , Hanitriniaina Rabeony b , Jean-Claude Lecron b, d , Christine Silvain a, b a Department of Hepato-Gastroenterology, Poitiers University Hospital, 86021 Poitiers, France b Laboratoire Inflammation Tissus Epith eliaux et Cytokines EA 4331, P^ ole Biologie Sant e, 86022 Poitiers, France c Department of Radiology, Poitiers University Hospital, 86000 Poitiers, France d Department of Immunology/Inflammation, Poitiers University Hospital, 86021 Poitiers, France article info Article history: Available online 6 September 2014 Keywords: Acute pancreatitis Cytokines IL-22 Necrosis infection IL-10 IL-1ra abstract Background/objectives: Pancreatic acinar cells are major targets of IL-22. Our aim is to study early plasma levels of IL-22, of pro- and anti-inflammatory cytokines in acute pancreatitis, and their association with severity or necrosis infection. Methods: Consecutive patients admitted to the Department of Hepato-Gastroenterology at Poitiers University of Medicine Hospital (France) with a diagnosis of AP were prospectively enrolled. Plasma concentrations of IL-22, IL-6, IL-8, IL-1 a, IL-1b, TNF- a, IFN-g, IL-17A, IL-10, IL-1ra and IL-4 were assessed by multiple immunoassay at the admission time. A thoracoabdominal contrast-enhanced CT scan was performed at day 2. Results: Sixty-two patients were included; 13 patients (21%) had a severe acute pancreatitis, 5 patients (8%) developed necrosis infection and 29 patients (47%) had pleural effusion. Plasma levels of IL-22 were high in AP (135 ± 31 vs 4.2 ± 1.8 pg/ml for controls, p < 0.05), but did not correlate with the severity of the disease, whereas IL-6, IL-10 and IL-1ra where enhanced in patients with severe acute pancreatitis and with pleural effusion. Patients who further developed necrosis infection had higher levels of IL-1ra at admission (p ¼ 0.0004). Conclusion: In acute pancreatitis, high plasma levels of IL-22 are observed, regardless the severity of the disease. In contrast, severe forms were associated with increased levels of IL-6, IL-10 and IL-1ra. The beneficial or deleterious role of IL-22 in AP remains to be further studied. Copyright © 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. Introduction During acute pancreatitis (AP), early prediction of severity is crucial as mortality reaches up to 30% in severe forms [1,2]. The early-phase mortality is related to organ dysfunctions, whereas necrosis infection is a critical complication that mainly occurs after 15 days of evolution [3]. Pro-inflammatory cytokines play a central role in amplifying both pancreatic and systemic inflammation, as shown by animal models of AP [4,5] and reflected by high circu- lating levels of IL-6, IL-8, IL-1b and TNF-a in severe acute pancre- atitis (SAP) [6,7]. Among the pro-inflammatory cytokines, IL-22, mainly produced by T helper 17 (Th17) cells and Th22 cells, is implicated in multiple tissue inflammation and defenses, especially against bacterial infections [8]. IL-22 signals through a dimeric re- ceptor comprising the broadly expressed IL-10R b chain associated to the IL-22R chain which exhibits a restricted expression pattern. Following IL-22 discovery, pancreatic acinar cells were identified as one of the first targets. IL-22 induces pancreatic associated protein 1 secretion in pancreatic acinar cells [9], suggesting its involvement in pancreatic inflammation. Relative to other human tissues, the highest IL-22R mRNA expression was reported in pancreas [10]. Nevertheless, to the best of our knowledge, IL-22 plasma levels have never been studied during AP. Abbreviations: AP, acute pancreatits; SAP, severe acute pancreatitis; IL, interleukine. * Corresponding author. Service d'h epato-gastroent erologie et assistance nutri- tive, CHU Jean Bernard, 2 rue de la Mil etrie e BP 577, 86021 Poitiers Cedex, France. Tel.: þ33 5 49 44 46 93; fax: þ33 5 49 44 38 35. E-mail address: philippe.vasseur@chu-poitiers.fr (P. Vasseur). Contents lists available at ScienceDirect Pancreatology journal homepage: www.elsevier.com/locate/pan http://dx.doi.org/10.1016/j.pan.2014.08.005 1424-3903/Copyright © 2014, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. Pancreatology 14 (2014) 465e469