Pancreatitis Independently Induced by Hypertriglyceridaemia Outlines the Immune Profiles of HTGP in Clinic

Abstract

Hypertriglyceridaemia (HTG) is a common and well-established aetiology of acute pancreatitis (AP). Although the underlying pathophysiology of hypertriglyceridaemic pancreatitis (HTGP) is complex, some animal models of HTAP have been successfully reproduced by repeated caerulein injections based on HTAP. However, most of the current HTGP models are critically dependent on the “two-attack” of cholecystokinin analogue, which may not be consistent with the fact of HTGP aetiologies due to ignored the initial effects of HTG in the development of HTGP. Here, we showed that HTGP could be induced by HTG independently, the HTGP mice with the typical characteristics and typical complications of pancreatitis. We found that the HTGP mice with mild pancreatic oedema, but the necrosis and immune cell infiltration were extensive. In addition, the immune cell infiltration and immune dysregulation that widely observed in HTGP patients were well reproduced in this model, including innate and adaptive immune cells. Our results suggest that the murine HTGP model independently induced by HTG could recapitulate the pathological and immunological profiles of HTGP in the clinic. More importantly, the model generated by this method could sustain a prolonged, non-life-threatening course of the disease and is suitable for research into the underlying mechanisms and for application to the preclinical evaluation of HTGP drugs.