mrjСовременная ревматологияModern Rheumatology Journal1996-70122310-158XIMA-PRESS, LLC10.14412/1996-7012-2009-518mrj-203Research ArticleСтатьиArticlesПерспективы применения микофенолата мофетила при системной склеродермииProspects for using mycophenolate mofetil in diffuse sclerodermaАнаньеваЛ. П.AnanyevaL P-20092503200931№1 (2009)2428Copyright © Ананьева Л.П., 20092009Ананьева Л.П.Ananyeva L.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://mrj.ima-press.net/mrj/article/view/203

Рассмотрены имуносупрессивные свойства микофенолата мофетила (ММФ) и результаты его использования при отторжении трансплантата и ревматических заболеваниях. Приведены данные, которые позволили предположить подавление избыточного фиброзообразования при использовании ММФ, а также результаты экспериментов, убедительно подтвердивших его антифиброзные свойства. Проанализированы результаты клинических испытаний ММФ при интерстициальном поражении легких у больных системной склеродермией, отмечены не только улучшение или стабилизация функциональных легочных тестов, но и оптимизация прогноза (по данным ретроспективных наблюдений). Интересны данные экспериментов, демонстрирующие подавление развития легочной гипертензии за счет антипролиферативных и противовоспалительных эффектов ММФ, которые свидетельствуют о потенциальных возможностях препарата в лечении легочной гипертензии.

The paper considers the immunosuppressive properties of micophenolate mofetil (MMF) and results of its use in graft rejection and rheumatic diseases. It also provides evidence suggesting the suppression of overfibrosis with the use of MMF, as well as the results of the experiments strongly confirming its antifibrotic properties. The author analyzes the results of clinical trials of MMF used in lung interstitial injury in patients with diffuse scleroderma, notes not only improvement or stabilization of lung functional tests, but also the optimization of prognosis (as evidenced by retrospective observations). Of interest are the experimental data demonstrating the suppression of pulmonary hypertension due to the antiproliferative and anti-inflammatory effects of MMF, which are indicative of the potential abilities of the agent to treat pulmonary hypertension.

References<div><p>Lin A.T., Clements P.J., Furst D.E. Update on disease modifying antirheumatic drugs in the treatment of systemic sclerosis. Rheum Dis Clin North Am 2003;29:409-26.</p><p>Shenin M., Naik M., Derk C.T. The use of mycophenolate mofetil for the treatment of systemic sclerosis. Endocr Metab Immune Disord Drug Targets 2008;8(1):11-4.</p><p>Blank N., Max R., Lorenz H.-M. The role of DMARDs in systemic sclerosis therapy Rheum 2006;45,iii42-44.</p><p>Marder W., McCune W.J. Advances in immunosuppressive therapy. Semin Respir Crit Care Med 2007;28(4):398-41.</p><p>Nannini C.,West C.P., Erwin P.J. Effects of cyclophosphamide on pulmonary function in patients with scleroderma and interstitial lung disease: a systematic review and meta-analysis of randomized controlled trials and observational prospective cohort studies. Res Ther 2008;10(5):R124.</p><p>Halloran P., Mathew T., Tomlanovich S. et al. Mycophenolate mofetil in renal allograft recipients. Transplantation 1997;63:39-47.</p><p>Sollinger H.W. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. Transplantation 1995;60:225-32.</p><p>Dooley M.A., Cosio F.G., Nachman P.H. et al. Mycophenolate mofetil therapy in lupus nephritis: clinical observation. J Am Soc Nephrol 1999;10:833-9.</p><p>Weir M.R., Fink J.C., Hanes D.S. et al. Chronic allograft nephropathy: effect of cyclosporine reduction and addition of mycophenolate mofetilon progression of renal disease. Transpl Proc 1999;31:1286-7.</p><p>Bardsley-Elliot A., Noble S., Foster R.H. Mycophenolate mofetil: a review of its use in the management of solid organ transplantation. BioDrugs 1999 Nov;12(5):363-410.</p><p>Blaheta R.A, Leckel K., Wittig B. et al. Mycophenolate mofetil impairs transendothelial migration of allogenic CD4 and CD8 T-cells. Transplant Proc 1999;31:1250-2.</p><p>Senda M., DeLustro B., Eugui E. et al. Mycophenolic acid, an ingibitor of IMP dehydrogenase that is also an immunosuppressive agent, suppresses the cytokine-induced nitric oxide production in mouse and rat vascular endothelial cells. Transplantation 1995;60:1143-8.</p><p>Клюквина Н.Г, Насонов Е.Л. Результаты десятилетнего применения микофенолата Мофетила при системных заболеваниях соединительной ткани. РМЖ 2007;15(26):1969-74.</p><p>Fujihara C.K., Malheiros DMAC., Zatz R. Mycophenolate mofetil attenuates renal injury in the rat ramnant kidney. Kidney Int 1998;54:1510-9.</p><p>Derk C.T., Jimenez S.A. Systemic sclerosis: current views of its pathogenesis. Autoimmun Rev 2003; 2:181-91.</p><p>Wallman L., Stewart G., Charman J. et al. Mycophenolate mofetil for treatment of refractory lupus nephritis: four pilot cases. Aust NZ J Med 2000;30:712-5.</p><p>Roos N., Poulalhon N., Farge D. et al. In Vitro Evidence for a direct antifibrotic Role of the Immunosupressive Drug Mycophenolate Mofetil. J Pharmacol Exper Therapeutics (JPET) 2007;321:583-9.</p><p>Tapia E., Franco M., Sanchez-Lozada L.G. et al. Mycophenolate mofetil prevents arteriolopathy and renal injury in subtotal ablation despite persistent hypertension. Kidney Int 2003;63(3):994-1002.</p><p>Rodriguez-Iturbe B., Pons H., Quiroz Y. et al. Mycophenolate mofetil prevents salt-sensitive hypertension resulting from angiotensin II exposure. Kidney Int.2001;59(6):2222-32.</p><p>Suzuki C., Takahashi M., Morimoto H. et al. Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats. Biochem Biophys Res Commun 2006,20;349(2):781-8.</p><p>IIkay E., Tirikli L., Ozercan I. et al. Oral Mycophenolat Mophetyl prevents in-stent intimal hyperplasia without edge effect Angiology 2006;57:577.</p><p>Stratton R.J., Wilson H., Black C.M. Pilot study of anti-thymocyte globulin plus mycophenolate mofetil in recent-onset diffuse scleroderma. Rheum 2001;40:84-8.</p><p>Liossis S.N.C., Bounas A., Andonopoulos A.P. Mycophenolate mofetil as first-line treatment improves clinically evident early sclero-derma lung disease Rheum 2006;45:1005-8.</p><p>Swigris J.J., Olson A.L., Fisher A. et al. Mycophenolate mofetil is safe, well tolerated, and preserves lung function in patients with connective tissue disease-related interstitial lung disease. Chest 2006;130:30-6.</p><p>Plastiras S.C., Vlachoyiannopoulos P.G., Tzelepis G.E. Mycophenolate mofetil for interstitial lung disease in scleroderma. Rheumatology 2006;45(12):1572.</p><p>Nihtyanova S.I., Brough G.M., Black C.M. et al. Mycophenolate mofetil in diffuse cutaneous systemic sclerosis - a retrospective analysis. Rheum 2007;46:442-5.</p><p>Vanthuyne M., Blockmans D., Westhovens R. et al. A pilot study of mycophenolate mofetil combined to intravenouse methylpred-nisolone pulses and oral low-dose glucocorti-coids in severe early systemic sclerosis. Clin Exp Rheumatol 2007;25(2):287-92.</p><p>Gerbino A.J., Goss C.H., Molitor J.A. Effect of mycophenolate mofetil on pulmonary function in scleroderma-associated interstitial lung disease. Chest 2008;Feb;133(2):455-60.</p><p>Zamora A.C., Wolters P.J., Collard H.R. et al. Use of mycophenolate mofetil to treat scle-roderma-associated interstitial lung disease. Respir Med 2008 Jan;102(1):150-5.</p><p>Корсакова Т.В. Применение селсепта для профилактики острого отторжения почечного трансплантата. Дис. ... канд. мед. наук. М., 1999.</p><p>Adu D., Cross J., Jayne D.R.W. Treatment of systemic lupus erythematosus with Mycophenolate mofetil. Lupus 2001;10:203-8.</p><p>Шекшина С.В. Применение циклоспорина А и мофетила микофенолата у больных системной красной волчанкой. Дис. . канд. мед. наук. М., 2002.</p></div><br /><div><p>Lin A.T., Clements P.J., Furst D.E. Update on disease modifying antirheumatic drugs in the treatment of systemic sclerosis. Rheum Dis Clin North Am 2003;29:409-26.</p><p>Shenin M., Naik M., Derk C.T. The use of mycophenolate mofetil for the treatment of systemic sclerosis. Endocr Metab Immune Disord Drug Targets 2008;8(1):11-4.</p><p>Blank N., Max R., Lorenz H.-M. The role of DMARDs in systemic sclerosis therapy Rheum 2006;45,iii42-44.</p><p>Marder W., McCune W.J. Advances in immunosuppressive therapy. Semin Respir Crit Care Med 2007;28(4):398-41.</p><p>Nannini C.,West C.P., Erwin P.J. Effects of cyclophosphamide on pulmonary function in patients with scleroderma and interstitial lung disease: a systematic review and meta-analysis of randomized controlled trials and observational prospective cohort studies. Res Ther 2008;10(5):R124.</p><p>Halloran P., Mathew T., Tomlanovich S. et al. Mycophenolate mofetil in renal allograft recipients. Transplantation 1997;63:39-47.</p><p>Sollinger H.W. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. Transplantation 1995;60:225-32.</p><p>Dooley M.A., Cosio F.G., Nachman P.H. et al. Mycophenolate mofetil therapy in lupus nephritis: clinical observation. J Am Soc Nephrol 1999;10:833-9.</p><p>Weir M.R., Fink J.C., Hanes D.S. et al. Chronic allograft nephropathy: effect of cyclosporine reduction and addition of mycophenolate mofetilon progression of renal disease. Transpl Proc 1999;31:1286-7.</p><p>Bardsley-Elliot A., Noble S., Foster R.H. Mycophenolate mofetil: a review of its use in the management of solid organ transplantation. BioDrugs 1999 Nov;12(5):363-410.</p><p>Blaheta R.A, Leckel K., Wittig B. et al. Mycophenolate mofetil impairs transendothelial migration of allogenic CD4 and CD8 T-cells. Transplant Proc 1999;31:1250-2.</p><p>Senda M., DeLustro B., Eugui E. et al. Mycophenolic acid, an ingibitor of IMP dehydrogenase that is also an immunosuppressive agent, suppresses the cytokine-induced nitric oxide production in mouse and rat vascular endothelial cells. Transplantation 1995;60:1143-8.</p><p>Клюквина Н.Г, Насонов Е.Л. Результаты десятилетнего применения микофенолата Мофетила при системных заболеваниях соединительной ткани. РМЖ 2007;15(26):1969-74.</p><p>Fujihara C.K., Malheiros DMAC., Zatz R. Mycophenolate mofetil attenuates renal injury in the rat ramnant kidney. Kidney Int 1998;54:1510-9.</p><p>Derk C.T., Jimenez S.A. Systemic sclerosis: current views of its pathogenesis. Autoimmun Rev 2003; 2:181-91.</p><p>Wallman L., Stewart G., Charman J. et al. Mycophenolate mofetil for treatment of refractory lupus nephritis: four pilot cases. Aust NZ J Med 2000;30:712-5.</p><p>Roos N., Poulalhon N., Farge D. et al. In Vitro Evidence for a direct antifibrotic Role of the Immunosupressive Drug Mycophenolate Mofetil. J Pharmacol Exper Therapeutics (JPET) 2007;321:583-9.</p><p>Tapia E., Franco M., Sanchez-Lozada L.G. et al. Mycophenolate mofetil prevents arteriolopathy and renal injury in subtotal ablation despite persistent hypertension. Kidney Int 2003;63(3):994-1002.</p><p>Rodriguez-Iturbe B., Pons H., Quiroz Y. et al. Mycophenolate mofetil prevents salt-sensitive hypertension resulting from angiotensin II exposure. Kidney Int.2001;59(6):2222-32.</p><p>Suzuki C., Takahashi M., Morimoto H. et al. Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats. Biochem Biophys Res Commun 2006,20;349(2):781-8.</p><p>IIkay E., Tirikli L., Ozercan I. et al. Oral Mycophenolat Mophetyl prevents in-stent intimal hyperplasia without edge effect Angiology 2006;57:577.</p><p>Stratton R.J., Wilson H., Black C.M. Pilot study of anti-thymocyte globulin plus mycophenolate mofetil in recent-onset diffuse scleroderma. Rheum 2001;40:84-8.</p><p>Liossis S.N.C., Bounas A., Andonopoulos A.P. Mycophenolate mofetil as first-line treatment improves clinically evident early sclero-derma lung disease Rheum 2006;45:1005-8.</p><p>Swigris J.J., Olson A.L., Fisher A. et al. Mycophenolate mofetil is safe, well tolerated, and preserves lung function in patients with connective tissue disease-related interstitial lung disease. Chest 2006;130:30-6.</p><p>Plastiras S.C., Vlachoyiannopoulos P.G., Tzelepis G.E. Mycophenolate mofetil for interstitial lung disease in scleroderma. Rheumatology 2006;45(12):1572.</p><p>Nihtyanova S.I., Brough G.M., Black C.M. et al. Mycophenolate mofetil in diffuse cutaneous systemic sclerosis - a retrospective analysis. Rheum 2007;46:442-5.</p><p>Vanthuyne M., Blockmans D., Westhovens R. et al. A pilot study of mycophenolate mofetil combined to intravenouse methylpred-nisolone pulses and oral low-dose glucocorti-coids in severe early systemic sclerosis. Clin Exp Rheumatol 2007;25(2):287-92.</p><p>Gerbino A.J., Goss C.H., Molitor J.A. Effect of mycophenolate mofetil on pulmonary function in scleroderma-associated interstitial lung disease. Chest 2008;Feb;133(2):455-60.</p><p>Zamora A.C., Wolters P.J., Collard H.R. et al. Use of mycophenolate mofetil to treat scle-roderma-associated interstitial lung disease. Respir Med 2008 Jan;102(1):150-5.</p><p>Корсакова Т.В. Применение селсепта для профилактики острого отторжения почечного трансплантата. Дис. ... канд. мед. наук. М., 1999.</p><p>Adu D., Cross J., Jayne D.R.W. Treatment of systemic lupus erythematosus with Mycophenolate mofetil. Lupus 2001;10:203-8.</p><p>Шекшина С.В. Применение циклоспорина А и мофетила микофенолата у больных системной красной волчанкой. Дис. . канд. мед. наук. М., 2002.</p></div><br />

The authors declare that there are no conflicts of interest present.