Department of Medicine, Division of Gastroenterology and Hepatology, University of Illinois at Chicago, Chicago, IL, USA.
Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, USA.
Sci Rep. 2017 Oct 6;7(1):12786. doi: 10.1038/s41598-017-13000-3.
Acute Pancreatitis is a substantial health care challenge with increasing incidence. Patients who develop severe disease have considerable mortality. Currently, no reliable predictive marker to identify patients at risk for severe disease exists. Treatment is limited to rehydration and supporting care suggesting an urgent need to develop novel approaches to improve standard care. Activin is a critical modulator of inflammatory responses, but has not been assessed in pancreatitis. Here, we demonstrate that serum activin is elevated and strongly correlates with disease severity in two established murine models of acute pancreatitis induced by either cerulein or IL-12 + IL-18. Furthermore, in mice, inhibition of activin conveys survival benefits in pancreatitis. In addition, serum activin levels were measured from a retrospective clinical cohort of pancreatitis patients and high activin levels in patients at admission are predictive of worse outcomes, indicated by longer overall hospital and intensive care unit stays. Taken together, activin is a novel candidate as a clinical marker to identify those acute pancreatitis patients with severe disease who would benefit from aggressive treatment and activin may be a therapeutic target in severe acute pancreatitis.
急性胰腺炎是一种具有发病率不断增加的重大医疗保健挑战。患有严重疾病的患者死亡率相当高。目前，尚无可靠的预测标志物来识别患有严重疾病的风险患者。治疗仅限于补液和支持性护理，这表明迫切需要开发新方法来改善标准护理。激活素是炎症反应的关键调节剂，但尚未在胰腺炎中进行评估。在这里，我们证明在两种通过 Cerulein 或 IL-12+IL-18 诱导的急性胰腺炎的既定小鼠模型中，血清激活素水平升高，并与疾病严重程度强烈相关。此外，在小鼠中，抑制激活素可在胰腺炎中提供生存益处。此外，还从胰腺炎患者的回顾性临床队列中测量了血清激活素水平，入院时高激活素水平预示着更差的结局，表明总住院时间和重症监护病房停留时间更长。总之，激活素是一种新的候选临床标志物，可用于识别那些患有严重疾病的急性胰腺炎患者，他们将从积极治疗中受益，而激活素可能是重症急性胰腺炎的治疗靶点。
