Interleukin-3 inhibition alleviates inflammation and tissue damage in severe acute pancreatitis: IL-3 and acute pancreatitis

Background and objective: Acute Pancreatitis (AP) is linked with leukocyte infiltration and tissue necrosis, however the cellular signaling pathways in pancreas which is leading to organ destruction remain unknown. IL-3 is a powerful controller of different cellular processes that promote pro-inflammatory activities. In this study, we investigated IL-3 signaling role of in acute pancreatitis. Methods: In C57BL/6 mice, pancreatitis was triggered by L-arginine injection (i.p.). Prior to development of pancreatitis, animals were given an IL-3 inhibitor (100 mg/kg). IL-6, MPO, and MIP-2 levels were measured by ELISA. Results: The administration of IL-3 significantly reduced the rise in L-arginine in serum amylase, pancreatic neutrophil infiltration, pancreatic edema formation, an acinar cell necrosis. Furthermore, in response to L-arginine challenge, inhibition of IL-3 caused a decrement in the MPO levels in both pancreas and lung (P <0.05). However, IL-3 therapy had a significant impact on L-arginine, provoked macrophage inflammatory protein-2 (MIP-2) induction in the pancreas. Interestingly, in vivo isolation of neutrophils revealed that inhibition of IL-3 significantly reduced MIP-2 and IL-6 pointing to a direct function for IL-3 in regulating chemokine and cytokine expression in neutrophils (P <0.05). Finally, trypsinogen activation induced by secretagogue in acinar calls of pancreas in vitro, was not directly affected by the inhibition of IL-3 (P >0.05). Conclusion: These findings show that IL-3 signaling has an essential role in acute pancreatitis by controlling tissue injury and neutrophil infiltration thus, in addition to clarifying pancreatitis signaling processes, our findings also raise the possibility that IL-3 can represent a new target in the treatment of severe AP.