Lung rejectionPirfenidone Inhibits Obliterative Airway Disease in Mouse Tracheal Allografts
Section snippets
Heterotopic Murine Animal Model
Sub-cutaneous tracheal transplantation was performed under general anesthesia in accordance with guidelines of the University of Florida Institutional Animal Care and Use Committee. All animals received humane care in compliance with The Principles of Laboratory Animal Care formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources. BALB/c and C57BL/6 8-week-old female mice were used as donors
Results
Rejection-associated histologic changes for this mouse trachea transplant model12 were evident to varying degrees in each group. The severity of these changes differed significantly between the untreated mice and mice treated with pirfenidone starting 1 day before transplant to time of killing, Day 16 or 28 post-transplant (Figure 1). Isografts demonstrated normal respiratory epithelium and no intraluminal granulation tissue. The majority of the allografts from the untreated animals showed a
Discussion
Transplantation-related chronic airway rejection, manifested as the histologic lesion of OB, is a fibroproliferative disorder and a major limitation to the long-term survival of lung transplant recipients.1, 2, 3 OB represents the result of immune-mediated, and possibly non–immune-mediated, small airway injury and is characterized histologically by fibrous luminal obliteration of small airways, lymphocytic airway infiltrates and respiratory epithelial sloughing and necrosis. Current medical
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Cited by (34)
Pirfenidone alleviates lung ischemia-reperfusion injury in a rat model
2019, Journal of Thoracic and Cardiovascular SurgeryCitation Excerpt :Furthermore, pirfenidone decreased the number of apoptotic cells and proinflammatory cytokines in lung tissue. There have been some reports that pirfenidone suppresses fibrosis caused by rejection and inflammatory change in the chronic or subacute phase after lung transplantation,16-18 but there are no reports of the acute phase, especially within 72 hours, after transplantation. In this study, it was shown that administration of pirfenidone was effective before the onset of lung IRI, which is the main cause of acute lung injury after lung transplantation.
Pirfenidone in restrictive allograft syndrome after lung transplantation: A case series
2018, American Journal of TransplantationUpdate in Chronic Lung Allograft Dysfunction
2017, Clinics in Chest MedicineCitation Excerpt :There are also data suggesting there may be a role for pirfenidone in lung transplant recipients. Preclinical data in animal models of transplant demonstrate a decrease in inflammation and fibrosis in animals treated with pirfenidone.139,140 There is 1 case report describing stabilization of lung function after use of pirfenidone in a patient with BOS.141
Pirfenidone ameliorates murine chronic GVHD through inhibition of macrophage infiltration and TGF-β production
2017, BloodCitation Excerpt :Pirfenidone (5-methyl-1-phenyl-2- (1H)-pyridone) is a small molecule known for its antifibrosis properties. In bleomycin-induced lung injury and lung allotransplant models, pirfenidone decreased hydroxyproline, fibrosis, procollagen I and II, platelet-derived growth factor isoforms, transforming growth factor-beta (TGF-β), fibroblast growth factor, and IL-13.13-21 Moreover, pirfenidone increases scavenger of reactive oxygen species22 and decreases inflammation pathways that initiate fibrosis, such as nitrites, IL-623 and tumor necrosis factor-α.24
Hepatocyte growth factor enhances the inflammation-alleviating effect of umbilical cord-derived mesenchymal stromal cells in a bronchiolitis obliterans model
2016, CytotherapyCitation Excerpt :The histopathologic features of this experimental BO model largely reproduce the changes in human recipients who develop BO after allogeneic HSCT. By using this model, investigations have been performed to testify various new strategies for the treatment of BO, such as interleukin (IL)-10 (DNAX Corp.)[7], Tacrolimus (Astellas Pharma) [4] and Pirfenidone (Marnac, Inc., Dallas, TX) [8]. Mesenchymal stromal cells (MSCs) are adult stem cells characterized by their immune-regulation properties.
Pirfenidone: A potential therapy for progressive lung allograft dysfunction?
2013, Journal of Heart and Lung Transplantation
Supported by a grant from the American Lung Association of Florida (to G.V.).