Mammalian Target of Rapamycin Inhibitors Vs Calcineurin Inhibitors in Chronic Graft Rejection After Lung Transplantation: A Systematic Review and Meta‐Analysis

Souza, Andressa Rodrigues de; Santos, Thulssa Auxiliadora Gomes Medeiros dos; Jakitsch, Camila Bomfim von; Sant’Anna, Ana Lúcia Gargione Galvão de; Claudio, João Carlos; Branco, João Nelson Rodrigues; Giovanazzi, Rosemeire Simone Dellacrode; Hossne, Nelson Américo; Pimentel, Walace de Souza; Costa, Suelen Alves Creste Martins da; Gironés, P.; Machado, Regimar Carla

doi:10.1016/j.transproceed.2021.09.019

Cited by 3 publications

(1 citation statement)

References 49 publications

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“…mTOR inhibitors are potent inhibitors of fibroblast proliferation, so there has also been interest in the use of these agents for the treatment and prevention of CLAD in lung transplant recipients. While some small studies have suggested potential benefit to mTOR inhibitors in preserving post-transplant lung function, larger studies and prospective trials have largely failed to show consistent benefit (85)(86)(87)(88)(89)(90)(91)(92)(93)(94). In a randomized, double-blind clinical trial, Snell et al randomized 213 BOS-free patients to everolimus or azathioprine in combination with cyclosporine and steroids, and found that change in FEV1 >15%, change in FEV1 >15% with BOS, and acute rejection were less common in everolimus group at 12 months (89).…”

Section: Mtor Inhibitorsmentioning

confidence: 99%

Immunosuppression in lung transplantation: a narrative review

Atkinson¹,

Sharma²

2023

Curr Chall Thorac Surg

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Background and Objective: Lung transplantation has grown as a treatment option for patients with end stage lung disease. Unfortunately, median survival for lung transplant recipients remains low at 6.7 years. Acute rejection and chronic lung allograft dysfunction (CLAD) are among the main challenges to graft function and overall survival. Immunosuppression is utilized to reduce the rate of rejection, and can be utilized as a treatment for acute rejection and CLAD. The purpose of this review is to describe the immunosuppressive agents used in lung transplantation for induction therapy, maintenance therapy, and prevention of both acute and chronic allograft rejection.Methods: PubMed was searched using keywords including "lung transplantation, immunosuppression, induction, maintenance" from January 1985 to June 2022. Systematic reviews, randomized clinical trials, retrospective and cross-sectional studies, case series, and some animal studies were considered for inclusion in this review, with no language restrictions.

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Section: Mtor Inhibitorsmentioning

confidence: 99%

Immunosuppression in lung transplantation: a narrative review

Atkinson¹,

Sharma²

2023

Curr Chall Thorac Surg

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The long-term effects of multidrug immunosuppressive protocols based on calcineurin inhibitors and conversion to rapamycin on the morphology, apoptosis, and proliferation of rat salivary glands

Grabowska,

Kędzierska-Kapuza,

Kram

et al. 2023

Pharmacol. Rep

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Background The effect of multidrug immunosuppressive protocols on the salivary glands is still unknown. This study aimed to determine the influence of immunosuppressive regimens based on calcineurin inhibitors (CNIs) and conversion to rapamycin on the morphology, apoptosis, and proliferation of rat salivary glands. Methods Male rats received cyclosporin A (CsA), tacrolimus (FK-506), mycophenolate mofetil (MMF), rapamycin (Rapa), and prednisone (Pre) according to three-drug protocols: CMP (CsA, MMF, and Pre), CMP/R (CsA, MMF, and Pre with conversion to Rapa), TMP (FK-506, MMF, and Pre), and TMP/R (FK-506, MMF, and Pre with conversion to Rapa). Morphological and immunohistochemical and quantitative analyses of the salivary glands were performed. Results Structural changes in salivary glands were observed in all experimental groups, especially in the submandibular gland. In the salivary glands, the percentages of collagen fibers and TUNEL-, Ki67- and PCNA-positive cells were higher in the experimental groups vs. the control but were lower in the CMP/R and TMP/R groups vs. the CMP and TMP groups, with the exception of collagen fibers in the parotid gland in the TMP/R group vs. the TMP group. Conclusions Long-term administration of CNIs in triple regimens and after conversion to rapamycin monotherapy, causes morphological changes in the salivary glands of rats. Immunosuppressive treatment based on CNIs is associated with an increase in collagen accumulation. The effects of the conversion of treatment with CNIs to rapamycin in immunosuppressive protocols in rat salivary glands lead to decreased fibrosis, apoptosis, and proliferation. These changes may possibly prevent abnormalities resulting from the application of CNIs.

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The Long Scientific Journey of Sirolimus (Rapamycin): From the Soil of Easter Island (Rapa Nui) to Applied Research and Clinical Trials on β-Thalassemia and Other Hemoglobinopathies

Gambari,

Zuccato,

Cosenza

et al. 2023

Biology

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In this review article, we present the fascinating story of rapamycin (sirolimus), a drug able to induce γ-globin gene expression and increased production of fetal hemoglobin (HbF) in erythroid cells, including primary erythroid precursor cells (ErPCs) isolated from β-thalassemia patients. For this reason, rapamycin is considered of great interest for the treatment of β-thalassemia. In fact, high levels of HbF are known to be highly beneficial for β-thalassemia patients. The story of rapamycin discovery began in 1964, with METEI, the Medical Expedition to Easter Island (Rapa Nui). During this expedition, samples of the soil from different parts of the island were collected and, from this material, an antibiotic-producing microorganism (Streptomyces hygroscopicus) was identified. Rapamycin was extracted from the mycelium with organic solvents, isolated, and demonstrated to be very active as an anti-bacterial and anti-fungal agent. Later, rapamycin was demonstrated to inhibit the in vitro cell growth of tumor cell lines. More importantly, rapamycin was found to be an immunosuppressive agent applicable to prevent kidney rejection after transplantation. More recently, rapamycin was found to be a potent inducer of HbF both in vitro using ErPCs isolated from β-thalassemia patients, in vivo using experimental mice, and in patients treated with this compound. These studies were the basis for proposing clinical trials on β-thalassemia patients.

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Mammalian Target of Rapamycin Inhibitors Vs Calcineurin Inhibitors in Chronic Graft Rejection After Lung Transplantation: A Systematic Review and Meta‐Analysis

Cited by 3 publications

References 49 publications

Immunosuppression in lung transplantation: a narrative review

Immunosuppression in lung transplantation: a narrative review

The long-term effects of multidrug immunosuppressive protocols based on calcineurin inhibitors and conversion to rapamycin on the morphology, apoptosis, and proliferation of rat salivary glands

The Long Scientific Journey of Sirolimus (Rapamycin): From the Soil of Easter Island (Rapa Nui) to Applied Research and Clinical Trials on β-Thalassemia and Other Hemoglobinopathies

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