Administration of anti-reg I and anti-PAPII antibodies worsens pancreatitis

Context: The regeneration protein family (Reg), which includes Reg I and PAPII, is expressed in pancreas acinar cells, and increases in acute pancreatitis. We have demonstrated that Reg gene knockdown worsens severity of acute pancreatitis in the rat and hypothesize that the proteins offer a protective effect in this disease. Objective: We investigated the ability of anti-Reg and anti-PAP antibody to neutralize pancreatic Reg protein and affect pancreatitis severity. Intervention Pancreatitis was induced in rats by retrograde ductal injection of 4% sodium taurocholate. Animals Eighty-four rats: 48 with induced pancreatitis, 30 sham operated, and 6 normal animals. Setting: Intraductal anti-Reg I and/or anti-PAPII antibody was administered at induced pancreatitis and sham operated subgroups of 6 rats each. Main outcome measure: Serum and pancreata were harvested 24 and/or 48 hours later and assessed for pancreatitis severity by pancreatic wet weight, serum C-reactive protein (CRP), amylase, PAPII levels, and histopathology. Results: Animals induced with pancreatitis with administration of anti-Reg/PAP antibodies had significantly higher wet weights compared with taurocholate and histopathological analysis revealed that anti-Reg/ PAP treated animals had worse tissue inflammation and necrosis compared with controls. Serum CRP, amylase, and Reg levels did not significantly differ between experimental and sham control groups. Conclusions: Administration of anti-Reg/PAP antibody worsened taurocholate-induced organ specific pancreatitis. These data suggest that the Reg family of proteins is protective in acute pancreatitis.