吡非尼酮
医学
急性胰腺炎
特发性肺纤维化
胰腺炎
内科学
胃肠病学
肺
作者
Ejas Palathingal Bava,John E. George,Mohd Tarique,Srikanth Iyer,Preeti Sahay,Beatriz Gomez Aguilar,Dujon Edwards,Bhuwan Giri,Vrishketan Sethi,Tejeshwar Jain,Prateek Sharma,Utpreksha Vaish,Harrys K.C. Jacob,Anthony Ferrantella,Craig L. Maynard,Ashok K. Saluja,Rajinder Dawra,Vikas Dudeja
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2022-01-25
卷期号:7 (2)
被引量:13
标识
DOI:10.1172/jci.insight.141108
摘要
Despite decades of research, there is no specific therapy for acute pancreatitis (AP). In the current study, we have evaluated the efficacy of pirfenidone, an antiinflammatory and antifibrotic agent that is approved by the FDA for treatment of idiopathic pulmonary fibrosis (IPF), in ameliorating local and systemic injury in AP. Our results suggest that treatment with pirfenidone in therapeutic settings (e.g., after initiation of injury), even when administered at the peak of injury, reduces severity of local and systemic injury and inflammation in multiple models of AP. In vitro evaluation suggests that pirfenidone decreases cytokine release from acini and macrophages and disrupts acinar-macrophage crosstalk. Therapeutic pirfenidone treatment increases IL-10 secretion from macrophages preceding changes in histology and modulates the immune phenotype of inflammatory cells with decreased levels of inflammatory cytokines. Antibody-mediated IL-10 depletion, use of IL-10-KO mice, and macrophage depletion experiments confirmed the role of IL-10 and macrophages in its mechanism of action, as pirfenidone was unable to reduce severity of AP in these scenarios. Since pirfenidone is FDA approved for IPF, a trial evaluating the efficacy of pirfenidone in patients with moderate to severe AP can be initiated expeditiously.
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