ObjectiveTo investigate the effects of generic interleukin (IL)-17A gene knockout (IL-17AKO) on pancreatic and intestinal barrier on acute pancreatitis (AP) in mice. MethodsIL-17AKO mice and their wild type (WT) littermates were employed to induce AP using cerulein (CER) and sodium taurocholate (NaTC). In the CER-AP experiment, mice were randomly divided into three groups: WT control group, WT model group, and IL-17AKO model group (n=5). Mice in the model group were intraperitoneally injected with CER [50 μg/(kg·h), 7 injections], and control group received intraperitoneal injection the same amount of 0.9% NaCl. The mice were sacrificed at 12 hours after the first injection of CER. The levels of serum amylase, lipase and IL-6 were detected, and the pancreas was stained with hematoxylin-eosin (HE). In the NaTC-AP experiment, WT mice were randomly divided into sham group (n=3) and operation model group (n=6). Similarly, IL-17AKO mice were also randomly allocated to sham group (n=3) and operation model group (n=6). The mice in the sham group underwent a surgical procedure on the abdomen only, whereas in the model group, 50 μL 3.5% NaTC dissolved in saline solution was pumped into the pancreatobiliary duct. Serum amylase, lipase, and IL-6 levels were detected. Pancreas was stained with HE, and intestine was stained with Alcian blue-periodic acid-Schiff, Dolichos Biflorus Agglutinin and bacteria fluorescence in situ hybridization. ResultsIn the CER-AP experiment, there were no significant differences in serum amylase, lipase, IL-6, and pathological changes including edema, inflammation, necrosis, and total pathological score of the pancreas between IL-17AKO and WT mice (P>0.05). In the NaTC-AP experiment, compared to the WT model group, IL-17AKO did not significantly impact serum amylase, lipase, and pancreatic pathological changes (P>0.05). However, it did lead to an increased level of IL-6 (P<0.05), and showed no significant protective effect on intestinal injury in NaTC-AP. Compared to WT mice of sham group, IL-17AKO mice of sham group exhibited decreased expressions of glycosylated mucin in ileum and colon, disordered mucus layer structure, and increased bacterial invasion. ConclusionsIL-17AKO has no significant protective effect on pancreatic and intestinal barrier damage in AP mice. Furthermore, it was discovered that prior to modeling, IL-17AKO mice exhibited higher bacterial invasion, intestinal barrier disruption, and a systemic inflammatory response. These findings imply that IL-17A plays a crucial role in immune responses and the maintenance of physiological intestinal barrier function in mice.