rIL-22 Alleviates Severe Acute Pancreatitis and Secondary Multiple Organ Injury Induced by Caerulein in Mice

Severe acute pancreatitis (SAP) is an inflammatory pancreatic disease characterized by significant tissue damage and systemic inflammation, leading to multiple organ failure and even death. IL-22 has been shown to have anti-inflammatory properties, but whether it can exert a protective effect in cases of multiple organ failure in SAP remains unclear. Therefore, this study aimed to systematically evaluate the protective effect of recombinant Interleukin (IL)-22 (rIL-22) on SAP and secondary multiple organ injury and the underlying mechanism for this effect. Balb/c mice were i.p. injected with caerulein (CAE) to induce SAP, followed by i.p. administration of rIL-22. Histopathological changes were observed by H&E staining. The serum levels of pancreatitis-related biomarkers and serum pro-inflammatory cytokines were measured. TUNEL assay was conducted to assess the number of apoptotic cells. The expression of pro-inflammatory cytokines, autophagy and apoptosis biomarkers were analyzed by IHC and Western blot. Rat pancreatic acinar cells (AR42J), Human non-small cell lung cancer cells (A549) and Human colon carcinoma cell lines (Caco-2) were stimulated with MDK83190 and Rapamycin to establish in vitro apoptosis and autophagy models. These models were then treated with rIL-22. Our data revealed pathological damage and dysfunction in the pancreas and multiple organs (including the liver, lungs, kidneys and colon), along with systemic inflammation, in CAE-induced SAP mice. Additionally, elevated levels of apoptosis and autophagy were detected in both the pancreas and multiple organs. Strikingly, rIL-22 alleviates SAP and secondary multiple organ damage, especially in the lungs and colon, by mitigating histopathological injury, reducing serum levels of pancreatitis-related biomarkers and pro-inflammatory cytokines (both in tissue and serum), and suppressing apoptosis and autophagy. Further study demonstrated that rIL-22 could reverse apoptosis and autophagy induced by MDK83190 and Rapamycin in vitro. These results suggest rIL-22 as a potential therapeutic candidate for SAP and its subsequent multiple organ injury.