Skip to main content
Erschienen in: Drugs 11/2013

01.07.2013 | Review Article

Adverse Effects of Immunosuppressant Drugs upon Airway Epithelial Cell and Mucociliary Clearance: Implications for Lung Transplant Recipients

verfasst von: Rogerio Pazetti, Paulo Manuel Pêgo-Fernandes, Fabio Biscegli Jatene

Erschienen in: Drugs | Ausgabe 11/2013

Einloggen, um Zugang zu erhalten

Abstract

Optimal post-transplantation immunosuppression is critical to the survival of the graft and the patient after lung transplantation. Immunosuppressant agents target various aspects of the immune system to maximize graft tolerance while minimizing medication toxicities and side effects. The vast majority of patients receive maintenance immunosuppressive therapy consisting of a triple-drug regimen including a calcineurin inhibitor, a cell cycle inhibitor and a corticosteroid. Although these immunosuppressant drugs are frequently used after transplantation and to control inflammatory processes, limited data are available with regard to their effects on cells other than those from the immunological system. Notably, the airway epithelial cell is of interest because it may contribute to development of bronchiolitis obliterans through production of pro-inflammatory cytokines. This review focuses the current armamentarium of immunosuppressant drugs used after lung transplantation and their main side effects upon airway epithelial cells and mucociliary clearance.
Literatur
1.
Zurück zum Zitat Christie JD, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: 29th adult lung and heart-lung transplant report—2012. J Heart Lung Transpl. 2012;31(10):1073–86.CrossRef Christie JD, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: 29th adult lung and heart-lung transplant report—2012. J Heart Lung Transpl. 2012;31(10):1073–86.CrossRef
2.
Zurück zum Zitat Taylor JL, Palmer SM. Critical care perspective on immunotherapy in lung transplantation. J Intensive Care Med. 2006;21:327.PubMedCrossRef Taylor JL, Palmer SM. Critical care perspective on immunotherapy in lung transplantation. J Intensive Care Med. 2006;21:327.PubMedCrossRef
3.
Zurück zum Zitat Speich R, van der Bij W. Epidemiology and management of infections after lung transplantation. Clin Infect Dis. 2001;33(Suppl. 1):S58–65.PubMedCrossRef Speich R, van der Bij W. Epidemiology and management of infections after lung transplantation. Clin Infect Dis. 2001;33(Suppl. 1):S58–65.PubMedCrossRef
4.
Zurück zum Zitat Aguilar-Guisado M, Givald J, Ussetti P, et al. Pneumonia after lung transplantation in the Resitra cohort: a multicenter prospective study. Am J Transpl. 2007;7:1989–96.CrossRef Aguilar-Guisado M, Givald J, Ussetti P, et al. Pneumonia after lung transplantation in the Resitra cohort: a multicenter prospective study. Am J Transpl. 2007;7:1989–96.CrossRef
5.
Zurück zum Zitat Randell SH, Boucher RC. Effective mucus clearance is essential for respiratory health. Am J Resp Cell Mol Biol. 2006;35:20–8.CrossRef Randell SH, Boucher RC. Effective mucus clearance is essential for respiratory health. Am J Resp Cell Mol Biol. 2006;35:20–8.CrossRef
6.
Zurück zum Zitat Qu N, Vos P, Schelfhorst M, et al. Integrity of airway epithelium is essential against obliterative airway disease in transplanted rat tracheas. J Heart Lung Transpl. 2005;24:882–90.CrossRef Qu N, Vos P, Schelfhorst M, et al. Integrity of airway epithelium is essential against obliterative airway disease in transplanted rat tracheas. J Heart Lung Transpl. 2005;24:882–90.CrossRef
7.
Zurück zum Zitat Nakajima T, Palchevsky V, Perkins DL, Belperio JA, Finn PW. Lung transplantation: infection, inflammation, and the microbiome. Semin Immunopathol. 2011;33:135–56.PubMedCrossRef Nakajima T, Palchevsky V, Perkins DL, Belperio JA, Finn PW. Lung transplantation: infection, inflammation, and the microbiome. Semin Immunopathol. 2011;33:135–56.PubMedCrossRef
8.
Zurück zum Zitat Borthwick LA, Parker SM, Brougham KA, et al. Epithelial to mesenchymal transition (EMT) and airway remodelling after human lung transplantation. Thorax. 2009;64:770–7.PubMedCrossRef Borthwick LA, Parker SM, Brougham KA, et al. Epithelial to mesenchymal transition (EMT) and airway remodelling after human lung transplantation. Thorax. 2009;64:770–7.PubMedCrossRef
9.
Zurück zum Zitat Felton VM, Inge LJ, Willis BC, et al. Immunosuppression-induced bronchial epithelial–mesenchymal transition: a potential contributor to obliterative bronchiolitis. J Thorac Cardiovasc Surg. 2011;141:523–30.PubMedCrossRef Felton VM, Inge LJ, Willis BC, et al. Immunosuppression-induced bronchial epithelial–mesenchymal transition: a potential contributor to obliterative bronchiolitis. J Thorac Cardiovasc Surg. 2011;141:523–30.PubMedCrossRef
10.
Zurück zum Zitat Neuringer IP, Sloan J, Budd S, et al. Calcineurin inhibitor effects on growth and phenotype of human airway epithelial cells in vitro. Am J Transpl. 2005;5:2660–70.CrossRef Neuringer IP, Sloan J, Budd S, et al. Calcineurin inhibitor effects on growth and phenotype of human airway epithelial cells in vitro. Am J Transpl. 2005;5:2660–70.CrossRef
11.
Zurück zum Zitat Azzola A, Havryk A, Chhajed P, et al. Everolimus and mycophenolate mofetil are potent inhibitors of fibroblast proliferation after lung transplantation. Transplantation. 2004;77:275–80.PubMedCrossRef Azzola A, Havryk A, Chhajed P, et al. Everolimus and mycophenolate mofetil are potent inhibitors of fibroblast proliferation after lung transplantation. Transplantation. 2004;77:275–80.PubMedCrossRef
12.
Zurück zum Zitat Pazetti R, Pêgo-Fernandes PM, Ranzani OT, et al. Cyclosporin A reduces airway mucus secretion and mucociliary clearance in rats. Clinics (São Paulo). 2007;62(3):345–52.CrossRef Pazetti R, Pêgo-Fernandes PM, Ranzani OT, et al. Cyclosporin A reduces airway mucus secretion and mucociliary clearance in rats. Clinics (São Paulo). 2007;62(3):345–52.CrossRef
13.
Zurück zum Zitat Pazetti R, Pêgo-Fernandes PM, Lorenzi-Filho G, et al. Effects of cyclosporine A and bronchial transection on mucociliary transport in rats. Ann Thorac Surg. 2008;85(6):1925–9 (discussion 1929). Pazetti R, Pêgo-Fernandes PM, Lorenzi-Filho G, et al. Effects of cyclosporine A and bronchial transection on mucociliary transport in rats. Ann Thorac Surg. 2008;85(6):1925–9 (discussion 1929).
14.
Zurück zum Zitat Pêgo-Fernandes PM, Said MM, Pazetti R, et al. Effects of azathioprine on mucociliary clearance after bronchial section and anastomosis in a rat experimental model. J Bras Pneumol. 2008;34(5):273–9.CrossRef Pêgo-Fernandes PM, Said MM, Pazetti R, et al. Effects of azathioprine on mucociliary clearance after bronchial section and anastomosis in a rat experimental model. J Bras Pneumol. 2008;34(5):273–9.CrossRef
15.
Zurück zum Zitat Silva VFP, Pazetti R, Soto SF, et al. Effects of mycophenolate sodium on mucociliary clearance using a bronchial section and anastomosis rodent model. Clinics. 2011;66(8):1451–5.PubMedCrossRef Silva VFP, Pazetti R, Soto SF, et al. Effects of mycophenolate sodium on mucociliary clearance using a bronchial section and anastomosis rodent model. Clinics. 2011;66(8):1451–5.PubMedCrossRef
16.
Zurück zum Zitat King MB, Jessurun J, Savik SK, et al. Cyclosporine reduces development of obliterative bronchiolitis in a murine heterotopic airway model. Transplantation. 1997;63(4):528–32.PubMedCrossRef King MB, Jessurun J, Savik SK, et al. Cyclosporine reduces development of obliterative bronchiolitis in a murine heterotopic airway model. Transplantation. 1997;63(4):528–32.PubMedCrossRef
17.
Zurück zum Zitat Ropponen JO, Syrjälä SO, Krebs R, et al. Innate and adaptive immune responses in obliterative airway disease in rat tracheal allografts. J Heart Lung Transpl. 2011;30:707–16.CrossRef Ropponen JO, Syrjälä SO, Krebs R, et al. Innate and adaptive immune responses in obliterative airway disease in rat tracheal allografts. J Heart Lung Transpl. 2011;30:707–16.CrossRef
18.
Zurück zum Zitat Yonan NA, Bishop P, El-Gamel A, et al. Tracheal allograft transplantation in rats: the role of immunosuppressive agents in development of obliterative airway disease. Transpl Proc. 1998;30:2207–9.CrossRef Yonan NA, Bishop P, El-Gamel A, et al. Tracheal allograft transplantation in rats: the role of immunosuppressive agents in development of obliterative airway disease. Transpl Proc. 1998;30:2207–9.CrossRef
19.
Zurück zum Zitat Deuse T, Schrepfer S, Koch-Nolte F, et al. FK778 and tacrolimus prevent the development of obliterative airway disease after heterotopic rat tracheal transplantation. J Heart Lung Transpl. 2005;24:1844–54.CrossRef Deuse T, Schrepfer S, Koch-Nolte F, et al. FK778 and tacrolimus prevent the development of obliterative airway disease after heterotopic rat tracheal transplantation. J Heart Lung Transpl. 2005;24:1844–54.CrossRef
20.
Zurück zum Zitat Schrepfer S, Deuse T, Sydow K, et al. Tracheal allograft transplantation in rats: the role of different immunosuppressants on preservation of respiratory epithelium. Transpl Proc. 2006;38(3):741–4.CrossRef Schrepfer S, Deuse T, Sydow K, et al. Tracheal allograft transplantation in rats: the role of different immunosuppressants on preservation of respiratory epithelium. Transpl Proc. 2006;38(3):741–4.CrossRef
21.
Zurück zum Zitat Matsumura Y, Marchevsky A, Zuo XJ, et al. Assessment of pathological changes associated with chronic allograft rejection and tolerance in two experimental models of rat lung transplantation. Transplantation. 1995;59:1509.PubMed Matsumura Y, Marchevsky A, Zuo XJ, et al. Assessment of pathological changes associated with chronic allograft rejection and tolerance in two experimental models of rat lung transplantation. Transplantation. 1995;59:1509.PubMed
22.
Zurück zum Zitat Uyama T, Winter JB, Groen G, et al. Late airway changes caused by chronic rejection in rat lung allografts. Transplantation. 1992;54:809.PubMedCrossRef Uyama T, Winter JB, Groen G, et al. Late airway changes caused by chronic rejection in rat lung allografts. Transplantation. 1992;54:809.PubMedCrossRef
23.
Zurück zum Zitat Schmid RA, Kwong K, Boasquevisque CH, et al. A chronic large animal model of lung allograft rejection. Transpl Proc. 1997;29:1521.CrossRef Schmid RA, Kwong K, Boasquevisque CH, et al. A chronic large animal model of lung allograft rejection. Transpl Proc. 1997;29:1521.CrossRef
24.
Zurück zum Zitat Xavier AM, Pêgo-Fernandes PM, Correia AT, et al. Influence of cyclosporine A on mucociliary system after lung transplantation in rats. Acta Cir Bras. 2007;22(6):465–9.PubMedCrossRef Xavier AM, Pêgo-Fernandes PM, Correia AT, et al. Influence of cyclosporine A on mucociliary system after lung transplantation in rats. Acta Cir Bras. 2007;22(6):465–9.PubMedCrossRef
25.
Zurück zum Zitat Bedi DS, Riella LV, Tullius SG, et al. Animal models of chronic allograft injury: contributions and limitations to understanding the mechanism of long-term graft dysfunction. Transplantation. 2010;90:935–44.PubMedCrossRef Bedi DS, Riella LV, Tullius SG, et al. Animal models of chronic allograft injury: contributions and limitations to understanding the mechanism of long-term graft dysfunction. Transplantation. 2010;90:935–44.PubMedCrossRef
26.
Zurück zum Zitat Deuse T, Schrepfer S, Reichenspurner H, et al. Techniques for experimental heterotopic and orthotopic tracheal transplantations—when to use which model? Transpl Immunol. 2007;17:255–61.PubMedCrossRef Deuse T, Schrepfer S, Reichenspurner H, et al. Techniques for experimental heterotopic and orthotopic tracheal transplantations—when to use which model? Transpl Immunol. 2007;17:255–61.PubMedCrossRef
27.
Zurück zum Zitat Borger P, Kauffman HF, Timmerman JAB, et al. Cyclosporine, FK506, mycophenolate mofetil, and prednisolone differentially modulate cytokine gene expression in human airway derived epithelial cells. Transplantation. 2000;69(7):1408–13.PubMedCrossRef Borger P, Kauffman HF, Timmerman JAB, et al. Cyclosporine, FK506, mycophenolate mofetil, and prednisolone differentially modulate cytokine gene expression in human airway derived epithelial cells. Transplantation. 2000;69(7):1408–13.PubMedCrossRef
28.
Zurück zum Zitat Floreth T, Stern E, Tu Y, et al. Differentiated transplant derived airway epithelial cell cytokine secretion is not regulated by cyclosporine. Respir Res. 2011;12:44.PubMedCrossRef Floreth T, Stern E, Tu Y, et al. Differentiated transplant derived airway epithelial cell cytokine secretion is not regulated by cyclosporine. Respir Res. 2011;12:44.PubMedCrossRef
29.
Zurück zum Zitat Kostakis A. Early experience with cyclosporine: a historic perspective. Transpl Proc. 2004;36(Suppl. 2S):22S–24S. Kostakis A. Early experience with cyclosporine: a historic perspective. Transpl Proc. 2004;36(Suppl. 2S):22S–24S.
30.
Zurück zum Zitat Bhorade SM, Stern E. Immunosuppression for lung transplantation. Proc Am Thorac Soc. 2009;6:47–53.PubMedCrossRef Bhorade SM, Stern E. Immunosuppression for lung transplantation. Proc Am Thorac Soc. 2009;6:47–53.PubMedCrossRef
31.
Zurück zum Zitat Parekh K, Trulock E, Patterson GA. Use of cyclosporine in lung transplantation. Transpl Proc. 2004;36(Suppl 2S):318S–322S. Parekh K, Trulock E, Patterson GA. Use of cyclosporine in lung transplantation. Transpl Proc. 2004;36(Suppl 2S):318S–322S.
32.
Zurück zum Zitat Treede H, Glanville AR, Klepetko W, et al. Tacrolimus and cyclosporine have differential effects on the risk of development of bronchiolitis obliterans syndrome: results of a prospective, randomized international trial in lung transplantation. J Heart Lung Transpl. 2012;31(8):797–804.CrossRef Treede H, Glanville AR, Klepetko W, et al. Tacrolimus and cyclosporine have differential effects on the risk of development of bronchiolitis obliterans syndrome: results of a prospective, randomized international trial in lung transplantation. J Heart Lung Transpl. 2012;31(8):797–804.CrossRef
33.
Zurück zum Zitat Akhlaghi F, Gonzalez L, Trull AK. Association between cyclosporine concentrations at 2 h post-dose and clinical outcomes in de novo lung transplant recipients. J Heart Lung Transpl. 2005;24(12):2120–8.CrossRef Akhlaghi F, Gonzalez L, Trull AK. Association between cyclosporine concentrations at 2 h post-dose and clinical outcomes in de novo lung transplant recipients. J Heart Lung Transpl. 2005;24(12):2120–8.CrossRef
34.
Zurück zum Zitat Masuda S, Inui K. An up-date review on individualized dosage adjustment of calcineurin inhibitors in organ transplant patients. Pharmacol Ther. 2006;112:184–98.PubMedCrossRef Masuda S, Inui K. An up-date review on individualized dosage adjustment of calcineurin inhibitors in organ transplant patients. Pharmacol Ther. 2006;112:184–98.PubMedCrossRef
35.
Zurück zum Zitat Malinowski M, Martus P, Lock JF, Neuhaus P, Stockmann M. Systemic influence of immunosuppressive drugs on small and large bowel transport and barrier function. Transpl Inter. 2011;24:184–93.CrossRef Malinowski M, Martus P, Lock JF, Neuhaus P, Stockmann M. Systemic influence of immunosuppressive drugs on small and large bowel transport and barrier function. Transpl Inter. 2011;24:184–93.CrossRef
36.
Zurück zum Zitat Hertz MI, Jessurun J, King MB, Savik SK, Murray JJ. Reproduction of the obliterative bronchiolitis lesion after heterotopic transplantation of mouse airways. Am J Pathol. 1993;142(6):1945–51.PubMed Hertz MI, Jessurun J, King MB, Savik SK, Murray JJ. Reproduction of the obliterative bronchiolitis lesion after heterotopic transplantation of mouse airways. Am J Pathol. 1993;142(6):1945–51.PubMed
37.
Zurück zum Zitat Adams BF, Berry GJ, Huang X, et al. Immunosuppressive therapies for the prevention and treatment of obliterative airway disease in heterotopic rat trachea allografts. Transplantation. 2000;69(11):2260–6.PubMedCrossRef Adams BF, Berry GJ, Huang X, et al. Immunosuppressive therapies for the prevention and treatment of obliterative airway disease in heterotopic rat trachea allografts. Transplantation. 2000;69(11):2260–6.PubMedCrossRef
38.
Zurück zum Zitat Koskinen PK, Kallio EA, Krebs R, et al. A dose-dependent inhibitory effect of cyclosporine A on obliterative bronchiolitis of rat tracheal allografts. Am J Respir Crit Care Med. 1997;155(1):303–12.PubMedCrossRef Koskinen PK, Kallio EA, Krebs R, et al. A dose-dependent inhibitory effect of cyclosporine A on obliterative bronchiolitis of rat tracheal allografts. Am J Respir Crit Care Med. 1997;155(1):303–12.PubMedCrossRef
39.
Zurück zum Zitat Takao M, Gu Y, Shimamoto A, Adachi K, Namikawa S, Yada I. Administration of exogenous interleukin-2 enhances obliterative airway disease in cyclosporine-treated rats following tracheal allografts. Transplant Proc. 1999;31:180–1.PubMedCrossRef Takao M, Gu Y, Shimamoto A, Adachi K, Namikawa S, Yada I. Administration of exogenous interleukin-2 enhances obliterative airway disease in cyclosporine-treated rats following tracheal allografts. Transplant Proc. 1999;31:180–1.PubMedCrossRef
40.
Zurück zum Zitat Neuringer I, Walsh S, Mannon R, Gabriel S, Aris RM. Enhanced T cell cytokine gene expression in mouse airway obliterative bronchiolitis. Transplantation. 2000;69(3):399–405.PubMedCrossRef Neuringer I, Walsh S, Mannon R, Gabriel S, Aris RM. Enhanced T cell cytokine gene expression in mouse airway obliterative bronchiolitis. Transplantation. 2000;69(3):399–405.PubMedCrossRef
41.
Zurück zum Zitat Fernández FG, Jaramillo A, Chen C, et al. Airway epithelium is the primary target of allograft rejection in murine obliterative airway disease. Am J Transpl. 2004;4(3):319–25.CrossRef Fernández FG, Jaramillo A, Chen C, et al. Airway epithelium is the primary target of allograft rejection in murine obliterative airway disease. Am J Transpl. 2004;4(3):319–25.CrossRef
42.
Zurück zum Zitat Delaere PR, Liu Z, Sciot R, Welvaart W. The role of immunosuppression in the long-term survival of tracheal allografts. Arch Otolaryngol Head Neck Surg. 1996;122(11):1201–8.PubMedCrossRef Delaere PR, Liu Z, Sciot R, Welvaart W. The role of immunosuppression in the long-term survival of tracheal allografts. Arch Otolaryngol Head Neck Surg. 1996;122(11):1201–8.PubMedCrossRef
43.
Zurück zum Zitat Genden EM, Boros P, Liu J, Bromberg JS, Mayer L. Orthotopic tracheal transplantation in the murine model. Transplantation. 2002;73(9):1420–5.PubMedCrossRef Genden EM, Boros P, Liu J, Bromberg JS, Mayer L. Orthotopic tracheal transplantation in the murine model. Transplantation. 2002;73(9):1420–5.PubMedCrossRef
44.
Zurück zum Zitat Padrid PA, Cozzi P, Leff AR. Cyclosporine A inhibits airway reactivity and remodeling after chronic antigen challenge in cats. Am J Respir Crit Care Med. 1996;154(6):1812–8.PubMedCrossRef Padrid PA, Cozzi P, Leff AR. Cyclosporine A inhibits airway reactivity and remodeling after chronic antigen challenge in cats. Am J Respir Crit Care Med. 1996;154(6):1812–8.PubMedCrossRef
45.
Zurück zum Zitat Iacono AT, Corcoran TE, Griffith BP, et al. Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans. Eur Respir J. 2004;23:384–90.PubMedCrossRef Iacono AT, Corcoran TE, Griffith BP, et al. Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans. Eur Respir J. 2004;23:384–90.PubMedCrossRef
46.
Zurück zum Zitat Waters V, Sokol S, Reddy B, et al. The effect of cyclosporin A on airway cell proinflammatory signaling and pneumonia. Am J Respir Cell Mol Biol. 2005;33:138–44.PubMedCrossRef Waters V, Sokol S, Reddy B, et al. The effect of cyclosporin A on airway cell proinflammatory signaling and pneumonia. Am J Respir Cell Mol Biol. 2005;33:138–44.PubMedCrossRef
47.
Zurück zum Zitat Aris RM, McNeillie P, Olusesi O, et al. Cyclosporine alters airway epithelial cell cytokine secretion: a potential mechanism to explain the efficacy of inhaled cyclosporine [abstract]. J Heart Lung Transpl. 2008;27:S206. Aris RM, McNeillie P, Olusesi O, et al. Cyclosporine alters airway epithelial cell cytokine secretion: a potential mechanism to explain the efficacy of inhaled cyclosporine [abstract]. J Heart Lung Transpl. 2008;27:S206.
48.
Zurück zum Zitat Hostettler KE, Roth M, Burgess JK, et al. Cyclosporine A mediates fibroproliferation through epithelial cells. Transplantation. 2004;77:1886–93.PubMedCrossRef Hostettler KE, Roth M, Burgess JK, et al. Cyclosporine A mediates fibroproliferation through epithelial cells. Transplantation. 2004;77:1886–93.PubMedCrossRef
49.
Zurück zum Zitat Ha EY, Mun KC. Effect of cyclosporine on apoptosis in bronchial epithelial cells. Transpl Proc. 2012;44:985–7.CrossRef Ha EY, Mun KC. Effect of cyclosporine on apoptosis in bronchial epithelial cells. Transpl Proc. 2012;44:985–7.CrossRef
50.
Zurück zum Zitat Jeon DS, Ha EY, Mun KC. Effects of cyclosporine on oxidative stress in human bronchial epithelial cells. Transpl Proc. 2012;44:988–90.CrossRef Jeon DS, Ha EY, Mun KC. Effects of cyclosporine on oxidative stress in human bronchial epithelial cells. Transpl Proc. 2012;44:988–90.CrossRef
51.
Zurück zum Zitat Reichenspurner H. Overview of tacrolimus-based immunosuppression after heart or lung transplantation. J Heart Lung Transpl. 2005;24:119–30.CrossRef Reichenspurner H. Overview of tacrolimus-based immunosuppression after heart or lung transplantation. J Heart Lung Transpl. 2005;24:119–30.CrossRef
52.
Zurück zum Zitat Snell GI, Westall GP. Immunosuppression for lung transplantation evidence to date. Drugs. 2007;67(11):1531–9.PubMedCrossRef Snell GI, Westall GP. Immunosuppression for lung transplantation evidence to date. Drugs. 2007;67(11):1531–9.PubMedCrossRef
53.
Zurück zum Zitat Scott LJ, McKeage K, Keam SJ, Plosker GL. Tacrolimus: a further update of its use in the management of organ transplantation. Drugs. 2003;63(12):1247–97.PubMedCrossRef Scott LJ, McKeage K, Keam SJ, Plosker GL. Tacrolimus: a further update of its use in the management of organ transplantation. Drugs. 2003;63(12):1247–97.PubMedCrossRef
54.
Zurück zum Zitat Watkins KD, Boettger RF, Hanger KM, et al. Use of sublingual tacrolimus in lung transplant recipients. J Heart Lung Transpl. 2012;31(2):127–32.CrossRef Watkins KD, Boettger RF, Hanger KM, et al. Use of sublingual tacrolimus in lung transplant recipients. J Heart Lung Transpl. 2012;31(2):127–32.CrossRef
55.
Zurück zum Zitat Schrepfer S, Deuse T, Reichenspurner H, et al. Effect of inhaled tacrolimus on cellular and humoral rejection to prevent posttransplant obliterative airway disease. Am J Transpl. 2007;7:1733–42.CrossRef Schrepfer S, Deuse T, Reichenspurner H, et al. Effect of inhaled tacrolimus on cellular and humoral rejection to prevent posttransplant obliterative airway disease. Am J Transpl. 2007;7:1733–42.CrossRef
56.
Zurück zum Zitat Deuse T, Blankenberg F, Haddad M, et al. Mechanisms behind local immunosuppression using inhaled tacrolimus in preclinical models of lung transplantation. Am J Respir Cell Mol Biol. 2010;43:403–12.PubMedCrossRef Deuse T, Blankenberg F, Haddad M, et al. Mechanisms behind local immunosuppression using inhaled tacrolimus in preclinical models of lung transplantation. Am J Respir Cell Mol Biol. 2010;43:403–12.PubMedCrossRef
57.
Zurück zum Zitat Hollmén M, Tikkanen JM, Nykänen AI, et al. Tacrolimus treatment effectively inhibits progression of obliterative airway disease even at later stages of disease development. J Heart Lung Transpl. 2008;27:856–64.CrossRef Hollmén M, Tikkanen JM, Nykänen AI, et al. Tacrolimus treatment effectively inhibits progression of obliterative airway disease even at later stages of disease development. J Heart Lung Transpl. 2008;27:856–64.CrossRef
58.
Zurück zum Zitat Hodge SJ, Hodge GL, Reynolds PN, et al. Differential rates of apoptosis in bronchoalveolar lavage and blood of lung transplant patients. J Heart Lung Transpl. 2005;24:1305–14.CrossRef Hodge SJ, Hodge GL, Reynolds PN, et al. Differential rates of apoptosis in bronchoalveolar lavage and blood of lung transplant patients. J Heart Lung Transpl. 2005;24:1305–14.CrossRef
59.
Zurück zum Zitat Hodge S, Hodge G, Ahern J, et al. Increased levels of T cell granzyme b in bronchiolitis obliterans syndrome are not suppressed adequately by current immunosuppressive regimens. Clin Exp Immunol. 2009;158:230–6.PubMedCrossRef Hodge S, Hodge G, Ahern J, et al. Increased levels of T cell granzyme b in bronchiolitis obliterans syndrome are not suppressed adequately by current immunosuppressive regimens. Clin Exp Immunol. 2009;158:230–6.PubMedCrossRef
60.
Zurück zum Zitat Evans JH, Sanderson MJ. Intracellular calcium oscillations regulate ciliary beat frequency of airway epithelial cells. Cell Calcium. 1999;26(3–4):103–10.PubMedCrossRef Evans JH, Sanderson MJ. Intracellular calcium oscillations regulate ciliary beat frequency of airway epithelial cells. Cell Calcium. 1999;26(3–4):103–10.PubMedCrossRef
61.
Zurück zum Zitat Bultynck G, De Smet P, Weidema AF, et al. Effects of the immunosuppressant FK506 on intracellular Ca2+ release and Ca2+ accumulation mechanisms. J Physiol. 2000;525(3):681–93.PubMedCrossRef Bultynck G, De Smet P, Weidema AF, et al. Effects of the immunosuppressant FK506 on intracellular Ca2+ release and Ca2+ accumulation mechanisms. J Physiol. 2000;525(3):681–93.PubMedCrossRef
62.
Zurück zum Zitat Kanoh S, Kondo M, Tamaoki J, et al. Effect of FK506 on ATP-induced intracellular calcium oscillations in cow tracheal epithelium. Am J Physiol. 1999;276:L891–9.PubMed Kanoh S, Kondo M, Tamaoki J, et al. Effect of FK506 on ATP-induced intracellular calcium oscillations in cow tracheal epithelium. Am J Physiol. 1999;276:L891–9.PubMed
63.
Zurück zum Zitat Maltzman JS, Koretzky GA. Azathioprine: old drug, new actions. J Clin Invest. 2003;111(8):1122–4.PubMed Maltzman JS, Koretzky GA. Azathioprine: old drug, new actions. J Clin Invest. 2003;111(8):1122–4.PubMed
64.
Zurück zum Zitat Taylor AL, Watson CJE, Bradley JA. Immunosuppressive agents in solid organ transplantation: mechanisms of action and therapeutic efficacy. Crit Rev Oncol Hematol. 2005;56(1):23–46.PubMedCrossRef Taylor AL, Watson CJE, Bradley JA. Immunosuppressive agents in solid organ transplantation: mechanisms of action and therapeutic efficacy. Crit Rev Oncol Hematol. 2005;56(1):23–46.PubMedCrossRef
65.
Zurück zum Zitat Hopkins PM, McNeil K. Evidence for immunosuppression in lung transplantation. Curr Opin Organ Transpl. 2008;13(5):477–83.CrossRef Hopkins PM, McNeil K. Evidence for immunosuppression in lung transplantation. Curr Opin Organ Transpl. 2008;13(5):477–83.CrossRef
66.
Zurück zum Zitat Maasilta PK, Salminen US, Lautenschlager I, Taskinen E, Harjula A. Immune cells and immunosuppression in a porcine bronchial model of obliterative bronchiolitis. Transplantation. 2001;72(6):998–1005.PubMedCrossRef Maasilta PK, Salminen US, Lautenschlager I, Taskinen E, Harjula A. Immune cells and immunosuppression in a porcine bronchial model of obliterative bronchiolitis. Transplantation. 2001;72(6):998–1005.PubMedCrossRef
67.
Zurück zum Zitat Snell GI, Levvey BJ, Zheng L, et al. Everolimus alters the bronchoalveolar lavage and endobronchial biopsy immunologic profile post-human lung transplantation. Am J Transpl. 2005;5:1446–51.CrossRef Snell GI, Levvey BJ, Zheng L, et al. Everolimus alters the bronchoalveolar lavage and endobronchial biopsy immunologic profile post-human lung transplantation. Am J Transpl. 2005;5:1446–51.CrossRef
68.
Zurück zum Zitat Kim HK, Rao VP, Park YS, et al. Pulmonary arterial reactivity during induced infection of single lung allografts. Eur J Cardiothorac Surg. 2007;31:475–81.PubMedCrossRef Kim HK, Rao VP, Park YS, et al. Pulmonary arterial reactivity during induced infection of single lung allografts. Eur J Cardiothorac Surg. 2007;31:475–81.PubMedCrossRef
69.
Zurück zum Zitat Snell GI, Levvey BJ, Zheng L, et al. Interleukin-17 and airway inflammation: a longitudinal airway biopsy study after lung transplantation. J Heart Lung Transpl. 2007;26:669–74.CrossRef Snell GI, Levvey BJ, Zheng L, et al. Interleukin-17 and airway inflammation: a longitudinal airway biopsy study after lung transplantation. J Heart Lung Transpl. 2007;26:669–74.CrossRef
70.
Zurück zum Zitat Palmer SM, Baz MA, Sanders L, et al. Results of a randomized prospective, multicenter trial of mycophenolate mofetil versus azathioprine in the prevention of acute lung allograft rejection. Transplantation. 2001;71:1772–6.PubMedCrossRef Palmer SM, Baz MA, Sanders L, et al. Results of a randomized prospective, multicenter trial of mycophenolate mofetil versus azathioprine in the prevention of acute lung allograft rejection. Transplantation. 2001;71:1772–6.PubMedCrossRef
71.
Zurück zum Zitat McNeil K, Glanville AR, Wahlers T, et al. Comparison of mycophenolate mofetil and azathioprine for prevention of bronchiolitis obliterans syndrome in de novo lung transplant recipients. Transplantation. 2006;81:998–1003.PubMedCrossRef McNeil K, Glanville AR, Wahlers T, et al. Comparison of mycophenolate mofetil and azathioprine for prevention of bronchiolitis obliterans syndrome in de novo lung transplant recipients. Transplantation. 2006;81:998–1003.PubMedCrossRef
72.
Zurück zum Zitat Bhorade S, Ahya VN, Baz MA, et al. Comparison of sirolimus with azathioprine in a tacrolimus-based immunosuppressive regimen in lung transplantation. Am J Respir Crit Care Med. 2011;183:379–87.PubMedCrossRef Bhorade S, Ahya VN, Baz MA, et al. Comparison of sirolimus with azathioprine in a tacrolimus-based immunosuppressive regimen in lung transplantation. Am J Respir Crit Care Med. 2011;183:379–87.PubMedCrossRef
73.
Zurück zum Zitat Snell GI, Valentine VG, Vitulo P, et al. Everolimus versus azathioprine in maintenance lung transplant recipients: an international, randomized, double-blind clinical trial. Am J Transpl. 2006;6:169–77.CrossRef Snell GI, Valentine VG, Vitulo P, et al. Everolimus versus azathioprine in maintenance lung transplant recipients: an international, randomized, double-blind clinical trial. Am J Transpl. 2006;6:169–77.CrossRef
74.
Zurück zum Zitat Knoop C, Haverich A, Fischer S. Immunosuppressive therapy after human lung transplantation. Eur Respir J. 2004;23:159–71.PubMedCrossRef Knoop C, Haverich A, Fischer S. Immunosuppressive therapy after human lung transplantation. Eur Respir J. 2004;23:159–71.PubMedCrossRef
75.
Zurück zum Zitat Korom S, Boehler A, Weder W. Immunosuppressive therapy in lung transplantation: state of the art. Eur J Cardiothorac Surg. 2009;35(6):1045–55.PubMedCrossRef Korom S, Boehler A, Weder W. Immunosuppressive therapy in lung transplantation: state of the art. Eur J Cardiothorac Surg. 2009;35(6):1045–55.PubMedCrossRef
76.
77.
Zurück zum Zitat He H, Ding H, Liao A, et al. Effects of mycophenolate mofetil on proliferation and mucin-5AC expression in human conjunctival goblet cells in vitro. Mol Vis. 2010;16:1913–9.PubMed He H, Ding H, Liao A, et al. Effects of mycophenolate mofetil on proliferation and mucin-5AC expression in human conjunctival goblet cells in vitro. Mol Vis. 2010;16:1913–9.PubMed
78.
Zurück zum Zitat Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000;47(2–3):85–118.PubMedCrossRef Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000;47(2–3):85–118.PubMedCrossRef
79.
Zurück zum Zitat Liu C, Schreiter T, Frilling A, et al. Cyclosporine A, FK-506, 40-0-[2-hydroxyethyl]rapamycin and mycophenolate mofetil inhibit proliferation of human intrahepatic biliary epithelial cells in vitro. World J Gastroenterol. 2005;11(48):7602–5.PubMed Liu C, Schreiter T, Frilling A, et al. Cyclosporine A, FK-506, 40-0-[2-hydroxyethyl]rapamycin and mycophenolate mofetil inhibit proliferation of human intrahepatic biliary epithelial cells in vitro. World J Gastroenterol. 2005;11(48):7602–5.PubMed
80.
Zurück zum Zitat Chen G, Korfhagen TR, Xu Y, et al. SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production. J Clin Invest. 2009;119(10):2914–24.PubMed Chen G, Korfhagen TR, Xu Y, et al. SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production. J Clin Invest. 2009;119(10):2914–24.PubMed
81.
Zurück zum Zitat Miljkovic DJ, Cvetkovic I, Stosic-Grujicic S, Trajkovic V. Mycophenolic acid inhibits activation of inducible nitric oxide synthase in rodent fibroblasts. Clin Exp Immunol. 2003;132:239–46.PubMedCrossRef Miljkovic DJ, Cvetkovic I, Stosic-Grujicic S, Trajkovic V. Mycophenolic acid inhibits activation of inducible nitric oxide synthase in rodent fibroblasts. Clin Exp Immunol. 2003;132:239–46.PubMedCrossRef
82.
Zurück zum Zitat Thompson ML, Flynn JD, Clifford TM. Pharmacotherapy of lung transplantation: an overview. J Pharm Pract. 2013;26(1):5–13.PubMedCrossRef Thompson ML, Flynn JD, Clifford TM. Pharmacotherapy of lung transplantation: an overview. J Pharm Pract. 2013;26(1):5–13.PubMedCrossRef
83.
Zurück zum Zitat Whitford H, Walters EH, Levvey B, et al. Addition of inhaled corticosteroids to systemic immunosuppression after lung transplantation: a double-blind, placebo-controlled trial. Transplantation. 2002;73(11):1793–9.PubMedCrossRef Whitford H, Walters EH, Levvey B, et al. Addition of inhaled corticosteroids to systemic immunosuppression after lung transplantation: a double-blind, placebo-controlled trial. Transplantation. 2002;73(11):1793–9.PubMedCrossRef
84.
Zurück zum Zitat Shah RV, Amin M, Sangwan S, et al. Steroid effects on mucociliary clearance in outpatient asthma. J Aerosol Med. 2006;19(2):208–20.PubMedCrossRef Shah RV, Amin M, Sangwan S, et al. Steroid effects on mucociliary clearance in outpatient asthma. J Aerosol Med. 2006;19(2):208–20.PubMedCrossRef
85.
Zurück zum Zitat Pujols L, Mullol J, Picado C. Glucocorticoid receptor in human respiratory epithelial cells. NeuroImmunomodulation. 2009;16(5):290–9.CrossRef Pujols L, Mullol J, Picado C. Glucocorticoid receptor in human respiratory epithelial cells. NeuroImmunomodulation. 2009;16(5):290–9.CrossRef
86.
Zurück zum Zitat Agnew JE, Bateman JR, Pavia D, Clarke SW. Peripheral airways mucus clearance in stable asthma is improved by oral corticosteroid therapy. Bull Eur Physiopathol Respir. 1984;20(3):295–301.PubMed Agnew JE, Bateman JR, Pavia D, Clarke SW. Peripheral airways mucus clearance in stable asthma is improved by oral corticosteroid therapy. Bull Eur Physiopathol Respir. 1984;20(3):295–301.PubMed
87.
Zurück zum Zitat Hanania NA, Chapman KR, Kesten S. Adverse effects of inhaled corticosteroids. Am J Med. 1995;98(2):196–208.PubMedCrossRef Hanania NA, Chapman KR, Kesten S. Adverse effects of inhaled corticosteroids. Am J Med. 1995;98(2):196–208.PubMedCrossRef
88.
Zurück zum Zitat Oliveira-Braga KA, Nepomuceno NA, Correia AT, Jatene FB, Pêgo-Fernandes PM. Effects of prednisone on mucociliary clearance in a murine model. Transpl Proc. 2012;44:2486–9.CrossRef Oliveira-Braga KA, Nepomuceno NA, Correia AT, Jatene FB, Pêgo-Fernandes PM. Effects of prednisone on mucociliary clearance in a murine model. Transpl Proc. 2012;44:2486–9.CrossRef
89.
Zurück zum Zitat Braga KAO, Nepomuceno NA, Correia AT, Jatene FB, Pêgo-Fernandes PM. The effects on mucociliary clearance of prednisone associated with bronchial section. Clinics. 2012;67(6):647–51.PubMedCrossRef Braga KAO, Nepomuceno NA, Correia AT, Jatene FB, Pêgo-Fernandes PM. The effects on mucociliary clearance of prednisone associated with bronchial section. Clinics. 2012;67(6):647–51.PubMedCrossRef
90.
Zurück zum Zitat Doerner AM, Zuraw BL. TGF-β1 induced epithelial to mesenchymal transition (EMT) in human bronchial epithelial cells is enhanced by IL-1β but not abrogated by corticosteroids. Respir Res. 2009;10:100.PubMedCrossRef Doerner AM, Zuraw BL. TGF-β1 induced epithelial to mesenchymal transition (EMT) in human bronchial epithelial cells is enhanced by IL-1β but not abrogated by corticosteroids. Respir Res. 2009;10:100.PubMedCrossRef
91.
Zurück zum Zitat Li CW, Shi L, Zhang KK, et al. Role of p63/p73 in epithelial remodeling and their response to steroid treatment in nasal polyposis. J Allergy Clin Immunol. 2011;127:765–72.PubMedCrossRef Li CW, Shi L, Zhang KK, et al. Role of p63/p73 in epithelial remodeling and their response to steroid treatment in nasal polyposis. J Allergy Clin Immunol. 2011;127:765–72.PubMedCrossRef
Metadaten
Titel
Adverse Effects of Immunosuppressant Drugs upon Airway Epithelial Cell and Mucociliary Clearance: Implications for Lung Transplant Recipients
verfasst von
Rogerio Pazetti
Paulo Manuel Pêgo-Fernandes
Fabio Biscegli Jatene
Publikationsdatum
01.07.2013
Verlag
Springer International Publishing
Erschienen in
Drugs / Ausgabe 11/2013
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-013-0089-0

Weitere Artikel der Ausgabe 11/2013

Drugs 11/2013 Zur Ausgabe