Anti-inflammatory and immunosuppressive agents in PAH

Handbook of Experimental Pharmacology

Volumn 218, Issue , 2013, Pages 437-476

  Meloche, Jolyane ^a,b   Renard, Sébastien ^a,b   Provencher, Steeve ^a,b   Bonnet, Sébastien ^a,b  

^a UNIVERSITÉ LAVAL   (Canada)

^b LAVAL UNIVERSITY   (Canada)

Author keywords

Immunosuppressive agents; Inflammatory mediators; PAH

Indexed keywords

ANTIBODY; ANTIINFLAMMATORY AGENT; ANTIRETROVIRUS AGENT; CYCLOPHOSPHAMIDE; CYCLOSPORIN A; DEXAMETHASONE; ENDOTHELIAL CELL ANTIBODY; ETANERCEPT; FIBROBLAST ANTIBODY; IMMUNOSUPPRESSIVE AGENT; METHOTREXATE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PRASTERONE; PRAZIQUANTEL; PREDNISONE; PROSTACYCLIN; RAPAMYCIN; UNCLASSIFIED DRUG;

ARTICLE; B LYMPHOCYTE; CONNECTIVE TISSUE DISEASE; DENDRITIC CELL; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG INTERACTION; HEART RIGHT VENTRICLE FAILURE; HERPES VIRUS INFECTION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFLAMMATION; LUNG BLOOD VESSEL; LUNG VASCULAR RESISTANCE; MACROPHAGE; MAST CELL; NONHUMAN; PATHOGENESIS; POEMS SYNDROME; PRIORITY JOURNAL; PULMONARY HYPERTENSION; PULMONARY VASCULAR DISEASE; SCHISTOSOMIASIS; SYSTEMIC LUPUS ERYTHEMATOSUS; SYSTEMIC SCLEROSIS; T LYMPHOCYTE;

ANIMALS; ANTI-INFLAMMATORY AGENTS; HUMANS; HYPERTENSION, PULMONARY; IMMUNOSUPPRESSIVE AGENTS; INFECTION; INFLAMMATION;

EID: 84893129805     PISSN: 01712004     EISSN: 18650325     Source Type: Book Series    
DOI: 10.1007/978-3-642-38664-0_18     Document Type: Article

References (235)

1. Actelion Pharmaceuticals (2011) Tracleer [package insert]. Actelion Pharmaceuticals US, Inc., South San Francisco, CA
2. Aramburu J, Yaffe MB, Lopez-Rodriguez C et al (1999) Affinity-driven peptide selection of an NFAT inhibitor more selective than cyclosporin A. Science 285:2129-2133
3. Arends SJ, Damoiseaux J, Duijvestijn A et al (2010) Prevalence of anti-endothelial cell antibodies in idiopathic pulmonary arterial hypertension. Eur Respir J 35:923-925
4. Ascherl G, Hohenadl C, Schatz O et al (1999) Infection with human immunodeficiency virus-1 increases expression of vascular endothelial cell growth factor in T cells: Implications for acquired immunodeficiency syndrome-associated vasculopathy. Blood 93:4232-4241
5. Asherson RA (1990) Pulmonary hypertension in systemic lupus erythematosus. J Rheumatol 17:414-415
6. Asherson RA, Oakley CM (1986) Pulmonary hypertension and systemic lupus erythematosus. J Rheumatol 13:1-5
7. Badesch DB, Champion HC, Sanchez MA et al (2009) Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol 54:S55-S66
8. Balabanian K, Foussat A, Dorfmuller P et al (2002) CX(3)C chemokine fractalkine in pulmonary arterial hypertension. Am J Respir Crit Care Med 165:1419-1425
9. Barile-Fabris L, Ariza-Andraca R, Olguin-Ortega L et al (2005) Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurological manifestations in systemic lupus erythematosus. Ann Rheum Dis 64:620-625
10. Barnier A, Frachon I, Dewilde J et al (2009) Improvement of HIV-related pulmonary hypertension after the introduction of an antiretroviral therapy. Eur Respir J 34:277-278
11. Barrier M, Meloche J, Jacob MH et al (2012) Today's and tomorrow's imaging and circulating biomarkers for pulmonary arterial hypertension. Cell Mol Life Sci 69(17):2805-2831
12. Bellotto F, Chiavacci P, Laveder F et al (1999) Effective immunosuppressive therapy in a patient with primary pulmonary hypertension. Thorax 54:372-374
13. Bendayan D, Sarid R, Cohen A et al (2008) Absence of human herpesvirus 8 DNA sequences in lung biopsies from Israeli patients with pulmonary arterial hypertension. Respiration 75:155-157
14. Bertsias G, Ioannidis JP, Boletis J et al (2008) EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis 67:195-205
15. Bhargava A, Kumar A, Yuan N et al (1999) Monocrotaline induces interleukin-6 mRNA expression in rat lungs. Heart Dis 1:126-132
16. Blyth KG, Groenning BA, Mark PB et al (2007) NT-proBNP can be used to detect right ventricular systolic dysfunction in pulmonary hypertension. Eur Respir J 29:737-744
17. Bogaard HJ, Abe K, Vonk Noordegraaf A et al (2009a) The right ventricle under pressure: Cellular and molecular mechanisms of right-heart failure in pulmonary hypertension. Chest 135:794-804
18. Bogaard HJ, Natarajan R, Henderson SC et al (2009b) Chronic pulmonary artery pressure elevation is insufficient to explain right heart failure. Circulation 120:1951-1960
19. Bokhari S, Raina A, Rosenweig EB et al (2011) PET imaging may provide a novel biomarker and understanding of right ventricular dysfunction in patients with idiopathic pulmonary arterial hypertension. Circ Cardiovasc Imaging 4:641-647
20. Bonnet S, Rochefort G, Sutendra G et al (2007) The nuclear factor of activated T cells in pulmonary arterial hypertension can be therapeutically targeted. Proc Natl Acad Sci USA 104:11418-11423
21. Bouree P, Piveteau J, Gerbal JL et al (1990) Pulmonary arterial hypertension due to bilharziasis. Apropos of a case due to Schistosoma haematobium having been cured by praziquantel. Bull Soc Pathol Exot 83:66-71
22. Brode S, Cooke A (2008) Immune-potentiating effects of the chemotherapeutic drug cyclophosphamide. Crit Rev Immunol 28:109-126
23. Bull TM, Cool CD, Serls AE et al (2003) Primary pulmonary hypertension, Castleman's disease and human herpesvirus-8. Eur Respir J 22:403-407
24. Butrous G, Ghofrani HA, Grimminger F (2008) Pulmonary vascular disease in the developing world. Circulation 118:1758-1766
25. Can MM, Kaymaz C, Tanboga IH et al (2011) Increased right ventricular glucose metabolism in patients with pulmonary arterial hypertension. Clin Nucl Med 36:743-748
26. Carneiro JR, Sato EI (1999) Double blind, randomized, placebo controlled clinical trial of methotrexate in systemic lupus erythematosus. J Rheumatol 26:1275-1279
27. Cerinic MM, Valentini G, Sorano GG et al (2003) Blood coagulation, fibrinolysis, and markers of endothelial dysfunction in systemic sclerosis. Semin Arthritis Rheum 32:285-295
28. Chizzolini C, Raschi E, Rezzonico R et al (2002) Autoantibodies to fibroblasts induce a proadhesive and proinflammatory fibroblast phenotype in patients with systemic sclerosis. Arthritis Rheum 46:1602-1613
29. Chu JW, Kao PN, Faul JL et al (2002) High prevalence of autoimmune thyroid disease in pulmonary arterial hypertension. Chest 122:1668-1673
30. Chung L, Liu J, Parsons L et al (2010) Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: Identifying systemic sclerosis as a unique phenotype. Chest 138:1383-1394
31. Clements PJ, Lachenbruch PA, Sterz M et al (1993) Cyclosporine in systemic sclerosis. Results of a forty-eight-week open safety study in ten patients. Arthritis Rheum 36:75-83
32. Cofan F, Gutierrez R, Beardo P et al (2002) Interaction between sildenafil and calcineurin inhibitors in renal transplant recipients with erectile dysfunction. Nefrologia 22:470-476
33. Coker RK (2007) Guidelines for the use of corticosteroids in the treatment of pulmonary sarcoidosis. Drugs 67:1139-1147
34. Condliffe R, Kiely DG, Peacock AJ et al (2009) Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era. Am J Respir Crit Care Med 179:151-157
35. Conejo-Garcia JR, Benencia F, Courreges MC et al (2004) Tumor-infiltrating dendritic cell precursors recruited by a beta-defensin contribute to vasculogenesis under the influence of Vegf-A. Nat Med 10:950-958
36. Contreras G, Pardo V, Leclercq B et al (2004) Sequential therapies for proliferative lupus nephritis. N Engl J Med 350:971-980
37. Cool CD, Kennedy D, Voelkel NF et al (1997) Pathogenesis and evolution of plexiform lesions in pulmonary hypertension associated with scleroderma and human immunodeficiency virus infection. Hum Pathol 28:434-442
38. Cool CD, Rai PR, Yeager ME et al (2003) Expression of human herpesvirus 8 in primary pulmonary hypertension. N Engl J Med 349:1113-1122
39. Crosby A, Jones FM, Southwood M et al (2010) Pulmonary vascular remodeling correlates with lung eggs and cytokines in murine schistosomiasis. Am J Respir Crit Care Med 181:279-288
40. Crosby A, Jones FM, Kolosionek E et al (2011) Praziquantel reverses pulmonary hypertension and vascular remodeling in murine schistosomiasis. Am J Respir Crit Care Med 184:467-473
41. Daley E, Emson C, Guignabert C et al (2008) Pulmonary arterial remodeling induced by a Th2 immune response. J Exp Med 205:361-372
42. de Almeida MA, Andrade ZA (1983) Effect of chemotherapy on experimental pulmonary schistosomiasis. Am J Trop Med Hyg 32:1049-1054
43. Deng Z, Morse JH, Slager SL et al (2000) Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet 67:737-744
44. Denton CP, Sweny P, Abdulla A et al (1994) Acute renal failure occurring in scleroderma treated with cyclosporin A: A report of three cases. Br J Rheumatol 33:90-92
45. Derk CT, Grace E, Shenin M et al (2009) A prospective open-label study of mycophenolate mofetil for the treatment of diffuse systemic sclerosis. Rheumatology (Oxford) 48:1595-1599
46. Dib H, Tamby MC, Bussone G et al (2011) Targets of anti-endothelial cell antibodies in pulmonary hypertension and scleroderma. Eur Respir J 39(6):1405-1414
47. Diller GP, van Eijl S, Okonko DO et al (2008) Circulating endothelial progenitor cells in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertension. Circulation 117:3020-3030
48. Dispenzieri A (2011) POEMS syndrome: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol 86:591-601
49. Dorfmuller P, Zarka V, Durand-Gasselin I et al (2002) Chemokine RANTES in severe pulmonary arterial hypertension. Am J Respir Crit Care Med 165:534-539
50. Dorfmuller P, Perros F, Balabanian K et al (2003) Inflammation in pulmonary arterial hypertension. Eur Respir J 22:358-363
51. Dorfmuller P, Humbert M, Perros F et al (2007) Fibrous remodeling of the pulmonary venous system in pulmonary arterial hypertension associated with connective tissue diseases. Hum Pathol 38:893-902
52. dos Santos Fernandes CJ, Jardim CV, Hovnanian A et al (2010) Survival in schistosomiasisassociated pulmonary arterial hypertension. J Am Coll Cardiol 56:715-720
53. Drake JI, Bogaard HJ, Mizuno S et al (2011) Molecular signature of a right heart failure program in chronic severe pulmonary hypertension. Am J Respir Cell Mol Biol 45:1239-1247
54. Drugs.com (2010) Side effects and drug-drug interaction. Denver, CO. http://www.drugs.com, Updated: 2010
55. Efferth T, Schwarzl SM, Smith J et al (2006) Role of glucose-6-phosphate dehydrogenase for oxidative stress and apoptosis. Cell Death Differ 13:527-528, author reply 529-530
56. Ehrenreich H, Rieckmann P, Sinowatz F et al (1993) Potent stimulation of monocytic endothelin-1 production by HIV-1 glycoprotein 120. J Immunol 150:4601-4609
57. Ensoli B, Barillari G, Salahuddin SZ et al (1990) Tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients. Nature 345:84-86
58. Fagan KA, Badesch DB (2002) Pulmonary hypertension associated with connective tissue disease. Prog Cardiovasc Dis 45:225-234
59. Fartoukh M, Emilie D, Le Gall C et al (1998) Chemokine macrophage inflammatory protein-1alpha mRNA expression in lung biopsy specimens of primary pulmonary hypertension. Chest 114:50S-51S
60. Fernandes CJ, Jardim CV, Hovnanian A et al (2011) Schistosomiasis and pulmonary hypertension. Expert Rev Respir Med 5:675-681
61. Filaci G, Cutolo M, Scudeletti M et al (1999) Cyclosporin A and iloprost treatment of systemic sclerosis: Clinical results and interleukin-6 serum changes after 12 months of therapy. Rheumatology (Oxford) 38:992-996
62. Fois E, Le Guern V, Dupuy A et al (2010) Noninvasive assessment of systolic pulmonary artery pressure in systemic lupus erythematosus: Retrospective analysis of 93 patients. Clin Exp Rheumatol 28:836-841
63. Freitas TC, Jung E, Pearce EJ (2007) TGF-beta signaling controls embryo development in the parasitic flatworm Schistosoma mansoni. PLoS Pathog 3:e52
64. Fritzler MJ, Hart DA, Wilson D et al (1995) Antibodies to fibrin bound tissue type plasminogen activator in systemic sclerosis. J Rheumatol 22:1688-1693
65. Fujita M, Shannon JM, Irvin CG et al (2001) Overexpression of tumor necrosis factor-alpha produces an increase in lung volumes and pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 280:L39-L49
66. Galie N, Hoeper MM, Humbert M et al (2009) Guidelines for the diagnosis and treatment of pulmonary hypertension: The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 30:2493-2537
67. Gan CT, McCann GP, Marcus JT et al (2006) NT-proBNP reflects right ventricular structure and function in pulmonary hypertension. Eur Respir J 28:1190-1194
68. Gerasimovskaya EV, Kratzer A, Sidiakova A et al (2012) Interplay of macrophages and T cells in the lung vasculature. Am J Physiol Lung Cell Mol Physiol 302(10):L1014-L1022
69. Gerbino AJ, Goss CH, Molitor JA (2008) Effect of mycophenolate mofetil on pulmonary function in scleroderma-associated interstitial lung disease. Chest 133:455-460
70. Goppelt-Struebe M, Wolter D, Resch K (1989) Glucocorticoids inhibit prostaglandin synthesis not only at the level of phospholipase A2 but also at the level of cyclo-oxygenase/PGE isomerase. Br J Pharmacol 98:1287-1295
71. Gourh P, Arnett FC, Assassi S et al (2009) Plasma cytokine profiles in systemic sclerosis: Associations with autoantibody subsets and clinical manifestations. Arthritis Res Ther 11:R147
72. Graham BB, Bandeira AP, Morrell NW et al 2010) Schistosomiasis-associated pulmonary hypertension: Pulmonary vascular disease: The global perspective. Chest 137:20S-29S
73. Grigolo B, Mazzetti I, Meliconi R et al (2000) Anti-topoisomerase II alpha autoantibodies in systemic sclerosis-association with pulmonary hypertension and HLA-B35. Clin Exp Immunol 121:539-543
74. Grinyo JM, Cruzado JM, Millan O et al (2004) Low-dose cyclosporine with mycophenolate mofetil induces similar calcineurin activity and cytokine inhibition as does standard-dose cyclosporine in stable renal allografts. Transplantation 78:1400-1403
75. Groen H, Bootsma H, Postma DS et al (1993) Primary pulmonary hypertension in a patient with systemic lupus erythematosus: Partial improvement with cyclophosphamide. J Rheumatol 20:1055-1057
76. Guignabert C, Izikki M, Tu LI et al (2006) Transgenic mice overexpressing the 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension. Circ Res 98:1323-1330
77. Guignabert C, Tu L, IzikkiMet al (2009) Dichloroacetate treatment partially regresses established pulmonary hypertension in mice with SM22alpha-targeted overexpression of the serotonin transporter. FASEB J 23:4135-4147
78. Hachulla E, Gressin V, Guillevin L et al (2005) Early detection of pulmonary arterial hypertension in systemic sclerosis: A French nationwide prospective multicenter study. Arthritis Rheum 52:3792-3800
79. Hachulla AL, Launay D, Gaxotte V et al (2009) Cardiac magnetic resonance imaging in systemic sclerosis: A cross-sectional observational study of 52 patients. Ann Rheum Dis 68:1878-1884
80. Hagen M, Fagan K, Steudel W et al (2007) Interaction of interleukin-6 and the BMP pathway in pulmonary smooth muscle. Am J Physiol Lung Cell Mol Physiol 292:L1473-L1479
81. Hall S, Brogan P, Haworth SG et al (2009) Contribution of inflammation to the pathology of idiopathic pulmonary arterial hypertension in children. Thorax 64:778-783
82. Hamada H, Terai M, Kimura H et al (1999) Increased expression of mast cell chymase in the lungs of patients with congenital heart disease associated with early pulmonary vascular disease. Am J Respir Crit Care Med 160:1303-1308
83. Hammer SM, Eron JJ Jr, Reiss P et al (2008) Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA 300:555-570
84. Hassoun PM (2009) Pulmonary arterial hypertension complicating connective tissue diseases. Semin Respir Crit Care Med 30:429-439
85. Hassoun PM, Mouthon L, Barbera JA et al (2009) Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol 54:S10-S19
86. Heath D, Yacoub M (1991) Lung mast cells in plexogenic pulmonary arteriopathy. J Clin Pathol 44:1003-1006
87. Heldin CH (1992) Structural and functional studies on platelet-derived growth factor. EMBO J 11:4251-4259
88. Henke-Gendo C, Mengel M, Hoeper MM et al (2005) Absence of Kaposi's sarcoma-associated herpesvirus in patients with pulmonary arterial hypertension. Am J Respir Crit Care Med 172:1581-1585
89. Henriques-Coelho T, Brandao-Nogueira A, Moreira-Goncalves D et al (2008) Effects of TNF-alpha blockade in monocrotaline-induced pulmonary hypertension. Rev Port Cardiol 27:341-348
90. Heresi GA, Minai OA (2007) Lupus-associated pulmonary hypertension: Long-term response to vasoactive therapy. Respir Med 101:2099-2107
91. Hoeper MM, Oudiz RJ, Peacock A et al (2004) End points and clinical trial designs in pulmonary arterial hypertension: Clinical and regulatory perspectives. J Am Coll Cardiol 43:48S-55S
92. Hoyles RK, Ellis RW, Wellsbury J et al (2006) A multicenter, prospective, randomized, doubleblind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma. Arthritis Rheum 54:3962-3970
93. Hsue PY, Deeks SG, Farah HH et al (2008) Role of HIV and human herpesvirus-8 infection in pulmonary arterial hypertension. AIDS 22:825-833
94. Huertas A, Tu L, Gambaryan N et al (2012) Leptin and regulatory T lymphocytes in idiopathic pulmonary arterial hypertension. Eur Respir J 40(4):895-904
95. Humbert M (2008) Mediators involved in HIV-related pulmonary arterial hypertension. AIDS 22 (Suppl 3):S41-S47
96. Humbert M, Monti G, Brenot F et al (1995) Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension. Am J Respir Crit Care Med 151:1628-1631
97. Humbert M, Monti G, Fartoukh M et al (1998) Platelet-derived growth factor expression in primary pulmonary hypertension: Comparison of HIV seropositive and HIV seronegative patients. Eur Respir J 11:554-559
98. Humbert M, Morrell NW, Archer SL et al (2004) Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 43:13S-24S
99. Imaizumi T, Yoshida H, Satoh K (2004) Regulation of CX3CL1/fractalkine expression in endothelial cells. J Atheroscler Thromb 11:15-21
100. Jais X, Launay D, Yaici A et al (2008) Immunosuppressive therapy in lupus-and mixed connective tissue disease-associated pulmonary arterial hypertension: A retrospective analysis of twentythree cases. Arthritis Rheum 58:521-531
101. Jouve P, Humbert M, Chauveheid MP et al (2007) POEMS syndrome-related pulmonary hypertension is steroid-responsive. Respir Med 101:353-355
102. Karmochkine M, Wechsler B, Godeau P et al (1996) Improvement of severe pulmonary hypertension in a patient with SLE. Ann Rheum Dis 55:561-562
103. Katayose D, Ohe M, Yamauchi K et al (1993) Increased expression of PDGF A-and B-chain genes in rat lungs with hypoxic pulmonary hypertension. Am J Physiol 264:L100-L106
104. Kawaguchi Y, Hara M, Harigai M et al (1998) Corticosteroid pulse therapy in a patient with SLE and pulmonary hypertension. Clin Exp Rheumatol 16:510
105. Kawut SM, Taichman DB, Archer-Chicko CL et al (2003) Hemodynamics and survival in patients with pulmonary arterial hypertension related to systemic sclerosis. Chest 123:344-350
106. Kherbeck N, Tamby MC, Bussone G et al (2011) The role of inflammation and autoimmunity in the pathophysiology of pulmonary arterial hypertension. Clin Rev Allergy Immunol 44 (1):31-38
107. King CH (2010) Parasites and poverty: The case of schistosomiasis. Acta Trop 113:95-104
108. Kobayashi T, Momoi Y, Iwasaki T (2007) Cyclosporine A inhibits the mRNA expressions of IL-2, IL-4 and IFN-gamma, but not TNF-alpha, in canine mononuclear cells. J Vet Med Sci 69:887-892
109. Koebel CM, Vermi W, Swann JB et al (2007) Adaptive immunity maintains occult cancer in an equilibrium state. Nature 450:903-907
110. Koulmann N, Novel-Chate V, Peinnequin A et al (2006) Cyclosporin A inhibits hypoxia-induced pulmonary hypertension and right ventricle hypertrophy. Am J Respir Crit Care Med 174:699-705
111. Kowal-Bielecka O, Landewe R, Avouac J et al (2009) EULAR recommendations for the treatment of systemic sclerosis: A report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis 68:620-628
112. Labarrere CA, Zaloga GP (2004) C-reactive protein: From innocent bystander to pivotal mediator of atherosclerosis. Am J Med 117:499-507
113. Lambertucci JR, Serufo JC, Gerspacher-Lara R et al (2000) Schistosoma mansoni: Assessment of morbidity before and after control. Acta Trop 77:101-109
114. Lane KB, Machado RD, Pauciulo MW et al (2000) Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nat Genet 26:81-84
115. Lapa M, Dias B, Jardim C et al (2009) Cardiopulmonary manifestations of hepatosplenic schistosomiasis. Circulation 119:1518-1523
116. Launay D, Souza R, Guillevin L et al (2006) Pulmonary arterial hypertension in ANCA-associated vasculitis. Sarcoidosis Vasc Diffuse Lung Dis 23:223-228
117. Launay D, Hachulla E, Hatron PY et al (2007) Pulmonary arterial hypertension: A rare complication of primary Sjogren syndrome: Report of 9 new cases and review of the literature. Medicine (Baltimore) 86:299-315
118. Le Pavec J, Humbert M, Mouthon L et al (2011) Systemic sclerosis-associated pulmonary arterial hypertension. Am J Respir Crit Care Med 181:1285-1293
119. Lesprit P, Godeau B, Authier FJ et al (1998) Pulmonary hypertension in POEMS syndrome: A new feature mediated by cytokines. Am J Respir Crit Care Med 157:907-911
120. Leung DY, Bloom JW (2003) Update on glucocorticoid action and resistance. J Allergy Clin Immunol 111:3-22, quiz 23
121. Lorenzen JM, Nickel N, Kramer R et al (2011) Osteopontin in patients with idiopathic pulmonary hypertension. Chest 139:1010-1017
122. Lovell DJ, Giannini EH, Reiff A et al (2000) Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. N Engl J Med 342:763-769
123. Luster AD (1998) Chemokines-chemotactic cytokines that mediate inflammation. N Engl J Med 338:436-445
124. Machado RD, Pauciulo MW, Thomson JR et al (2001) BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am J Hum Genet 68:92-102
125. Macian F (2005) NFAT proteins: Key regulators of T-cell development and function. Nat Rev Immunol 5:472-484
126. Mandagere A, Core B, Bird S, Bingham J, Boinpally R (2010) Absence of a clinically relevant pharmacokinetic interaction between ambrisentan and mycophenolate mofetil. In: American Journal of Respiratory and Critical Care Medicine. American Thoracic Society International Conference, New Orleans, LA, USA
127. Manno R, Boin F (2010) Immunotherapy of systemic sclerosis. Immunotherapy 2:863-878
128. Marder W, McCune WJ (2007) Advances in immunosuppressive therapy. Semin Respir Crit Care Med 28:398-417
129. Mathai SC, Hassoun PM (2011) Pulmonary arterial hypertension associated with systemic sclerosis. Expert Rev Respir Med 5:267-279
130. Mathai SC, Hummers LK, Champion HC et al (2009) Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: Impact of interstitial lung disease. Arthritis Rheum 60:569-577
131. McCune WJ, Golbus J, Zeldes W et al (1988) Clinical and immunologic effects of monthly administration of intravenous cyclophosphamide in severe systemic lupus erythematosus. N Engl J Med 318:1423-1431
132. McKinsey TA, Olson EN (2005) Toward transcriptional therapies for the failing heart: Chemical screens to modulate genes. J Clin Invest 115:538-546
133. McMurtry MS, Bonnet S, Wu X et al (2004) Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ Res 95:830-840
134. McMurtry MS, Bonnet S, Michelakis ED et al (2007) Statin therapy, alone or with rapamycin, does not reverse monocrotaline pulmonary arterial hypertension: The rapamycin-atorvastatinsimvastatin study. Am J Physiol Lung Cell Mol Physiol 293:L933-L940
135. Mehta NJ, Khan IA, Mehta RN et al (2000) HIV-Related pulmonary hypertension: Analytic review of 131 cases. Chest 118:1133-1141
136. Michelakis ED, McMurtry MS, Wu XC et al (2002) Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats: Role of increased expression and activity of voltage-gated potassium channels. Circulation 105:244-250
137. Minai OA (2009) Pulmonary hypertension in polymyositis-dermatomyositis: Clinical and hemodynamic characteristics and response to vasoactive therapy. Lupus 18:1006-1010
138. Montani D, Achouh L, Marcelin AG et al (2005a) Reversibility of pulmonary arterial hypertension in HIV/HHV8-associated Castleman's disease. Eur Respir J 26:969-972
139. Montani D, Marcelin AG, Sitbon O et al (2005b) Human herpes virus 8 in HIV and non-HIV infected patients with pulmonary arterial hypertension in France. AIDS 19:1239-1240
140. Montani D, Humbert M, Souza R (2011) Letter by Montani et al regarding article, Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension. Circulation 123:e614, author reply e615
141. Morelli S, Giordano M, De Marzio P et al (1993) Pulmonary arterial hypertension responsive to immunosuppressive therapy in systemic lupus erythematosus. Lupus 2:367-369
142. Morse JH, Barst RJ, Fotino M et al (1997) Primary pulmonary hypertension, tissue plasminogen activator antibodies, and HLA-DQ7. Am J Respir Crit Care Med 155:274-278
143. Mouthon L, Guillevin L, Humbert M (2005) Pulmonary arterial hypertension: An autoimmune disease Eur Respir J 26:986-988
144. Mukerjee D, Kingdon E, Vanderpump M et al (2003a) Pathophysiological insights from a case of reversible pulmonary arterial hypertension. J R Soc Med 96:403-404
145. Mukerjee D, St George D, Coleiro B et al (2003b) Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: Application of a registry approach. Ann Rheum Dis 62:1088-1093
146. Mutschler D, Wikstrom G, Lind L et al (2006) Etanercept reduces late endotoxin-induced pulmonary hypertension in the pig. J Interferon Cytokine Res 26:661-667
147. Nadashkevich O, Davis P, Fritzler M et al (2006) A randomized unblinded trial of cyclophosphamide versus azathioprine in the treatment of systemic sclerosis. Clin Rheumatol 25:205-212
148. Nagaya N, Nishikimi T, Uematsu M et al (2000) Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension. Circulation 102:865-870
149. Nannini C, West CP, Erwin PJ et al (2008) 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. Arthritis Res Ther 10:R124
150. Nathan C (2002) Points of control in inflammation. Nature 420:846-852
151. Negi VS, Tripathy NK, Misra R et al (1998) Antiendothelial cell antibodies in scleroderma correlate with severe digital ischemia and pulmonary arterial hypertension. J Rheumatol 25:462-466
152. Nicolls MR, Taraseviciene-Stewart L, Rai PR et al (2005) Autoimmunity and pulmonary hypertension: A perspective. Eur Respir J 26:1110-1118
153. Nishimura T, Faul JL, Berry GJ et al (2001) 40-O-(2-hydroxyethyl)- rapamycin attenuates pulmonary arterial hypertension and neointimal formation in rats. Am J Respir Crit Care Med 163:498-502
154. Niu X, Nouraie M, Campbell A et al (2009) Angiogenic and inflammatory markers of cardiopulmonary changes in children and adolescents with sickle cell disease. PLoS One 4:e7956
155. Nunes H, Humbert M, Sitbon O et al (2003) Prognostic factors for survival in human immunodeficiency virus-associated pulmonary arterial hypertension. Am J Respir Crit Care Med 167:1433-1439
156. Nunes H, Humbert M, Capron F et al (2006) Pulmonary hypertension associated with sarcoidosis: Mechanisms, haemodynamics and prognosis. Thorax 61:68-74
157. Ogawa A, Nakamura K, Matsubara H et al (2005) Prednisolone inhibits proliferation of cultured pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension. Circulation 112:1806-1812
158. Ogawa A, Nakamura K, Mizoguchi H et al (2011) Prednisolone ameliorates idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 183:139-140
159. Okano Y, Steen VD, Medsger TA Jr (1992) Autoantibody to U3 nucleolar ribonucleoprotein (fibrillarin) in patients with systemic sclerosis. Arthritis Rheum 35:95-100
160. Opravil M, Sereni D (2008) Natural history of HIV-associated pulmonary arterial hypertension: Trends in the HAART era. AIDS 22(Suppl 3):S35-S40
161. Opravil M, Pechere M, Speich R et al (1997) HIV-associated primary pulmonary hypertension. A case control study. Swiss HIV Cohort Study. Am J Respir Crit Care Med 155:990-995
162. Overbeek MJ, Lankhaar JW, Westerhof N et al (2008) Right ventricular contractility in systemic sclerosis-associated and idiopathic pulmonary arterial hypertension. Eur Respir J 31:1160-1166
163. Palucka AK, Blanck JP, Bennett L et al (2005) Cross-regulation of TNF and IFN-alpha in autoimmune diseases. Proc Natl Acad Sci USA 102:3372-3377
164. Paulin R, Meloche J, Jacob MH et al (2011) Dehydroepiandrosterone inhibits the Src/STAT3 constitutive activation in pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol 301:H1798-H1809
165. Pellicelli AM, Palmieri F, D'Ambrosio C et al (1998) Role of human immunodeficiency virus in primary pulmonary hypertension-case reports. Angiology 49:1005-1011
166. Perros F, Dorfmuller P, Souza R et al (2007) Dendritic cell recruitment in lesions of human and experimental pulmonary hypertension. Eur Respir J 29:462-468
167. Perros F, Montani D, Dorfmuller P et al (2011) [Novel immunopathological approaches to pulmonary arterial hypertension]. Presse Med 40(Suppl 1):1S3-1S13
168. Perros F, Dorfmuller P, Montani D et al (2012) Pulmonary lymphoid neogenesis in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 185:311-321
169. Piao L, Fang YH, Cadete VJ et al (2010a) The inhibition of pyruvate dehydrogenase kinase improves impaired cardiac function and electrical remodeling in two models of right ventricular hypertrophy: Resuscitating the hibernating right ventricle. J Mol Med (Berl) 88:47-60
170. Piao L, Marsboom G, Archer SL (2010b) Mitochondrial metabolic adaptation in right ventricular hypertrophy and failure. J Mol Med (Berl) 88:1011-1020
171. Pines A, Kaplinsky N, Goldhammer E et al (1982) Corticosteroid responsive pulmonary hypertension in systemic lupus erythematosus. Clin Rheumatol 1:301-304
172. Pope J (2008) An update in pulmonary hypertension in systemic lupus erythematosus-do we need to know about it Lupus 17:274-277
173. Pope JE, Bellamy N, Seibold JR et al (2001) A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma. Arthritis Rheum 44:1351-1358
174. Price LC, Montani D, Tcherakian C et al (2011) Dexamethasone reverses monocrotaline-induced pulmonary arterial hypertension in rats. Eur Respir J 37:813-822
175. Price LC, Wort SJ, Perros F et al (2012) Inflammation in pulmonary arterial hypertension. Chest 141:210-221
176. Pullamsetti SS, Savai R, JanssenWet al (2011) Inflammation, immunological reaction and role of infection in pulmonary hypertension. Clin Microbiol Infect 17:7-14
177. Quarck R, Nawrot T, Meyns B et al (2009) C-reactive protein: A new predictor of adverse outcome in pulmonary arterial hypertension. J Am Coll Cardiol 53:1211-1218
178. Quismorio FP Jr, Sharma O, Koss M et al (1984) Immunopathologic and clinical studies in pulmonary hypertension associated with systemic lupus erythematosus. Semin Arthritis Rheum 13:349-359
179. Rhen T, Cidlowski JA (2005) Antiinflammatory action of glucocorticoids-new mechanisms for old drugs. N Engl J Med 353:1711-1723
180. Ribeiro JM, Lucas M, Victorino RM (2001) Remission of precapillary pulmonary hypertension in systemic lupus erythematosus. J R Soc Med 94:32-33
181. Rich S, Kieras K, Hart K et al (1986) Antinuclear antibodies in primary pulmonary hypertension. J Am Coll Cardiol 8:1307-1311
182. Ross AG, Bartley PB, Sleigh AC et al (2002) Schistosomiasis. N Engl J Med 346:1212-1220
183. Rubin LJ (1997) Primary pulmonary hypertension. N Engl J Med 336:111-117
184. Ryan J, Bloch K, Archer SL (2011) Rodent models of pulmonary hypertension: Harmonisation with the world health organisation's categorisation of human PH. Int J Clin Pract Suppl (172):15-34
185. Salojin KV, Bordron A, Nassonov EL et al (1997) Anti-endothelial cell antibody, thrombomodulin, and von Willebrand factor in idiopathic inflammatory myopathies. Clin Diagn Lab Immunol 4:519-521
186. Sanchez O, Sitbon O, Jais X et al (2006) Immunosuppressive therapy in
187. Sanchez O, Marcos E, Perros F et al (2007) Role of endothelium-derived CC chemokine ligand 2 in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 176:1041-1047
188. Savale L, Tu L, Rideau D et al (2009) Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice. Respir Res 10:6
189. Schall TJ, Bacon K, Toy KJ et al (1990) Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature 347:669-671
190. Schall TJ, Bacon K, Camp RD et al (1993) Human macrophage inflammatory protein alpha (MIP-1 alpha) and MIP-1 beta chemokines attract distinct populations of lymphocytes. J Exp Med 177:1821-1826
191. Schermuly RT, Dony E, Ghofrani HA et al (2005) Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 115:2811-2821
192. Schwartz BG, Kloner RA (2010) Drug interactions with phosphodiesterase-5 inhibitors used for the treatment of erectile dysfunction or pulmonary hypertension. Circulation 122:88-95
193. Scirica BM, Morrow DA (2006) Is C-reactive protein an innocent bystander or proatherogenic culprit The verdict is still out. Circulation 113:2128-2134, discussion 2151
194. Sgonc R, Gruschwitz MS, Boeck G et al (2000) Endothelial cell apoptosis in systemic sclerosis is induced by antibody-dependent cell-mediated cytotoxicity via CD95. Arthritis Rheum 43:2550-2562
195. Shibasaki F, Fukami K, Fukui Y et al (1994) Phosphatidylinositol 3-kinase binds to alpha-actinin through the p85 subunit. Biochem J 302(Pt 2):551-557
196. Simonneau G, Robbins IM, Beghetti M et al (2009) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 54:S43-S54
197. Sitbon O, Lascoux-Combe C, Delfraissy JF et al (2008) Prevalence of HIV-related pulmonary arterial hypertension in the current antiretroviral therapy era. Am J Respir Crit Care Med 177:108-113
198. Song Y, Coleman L, Shi J et al (2008) Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice. Am J Physiol Heart Circ Physiol 295: H677-H690
199. Soon E, Holmes AM, Treacy CM et al (2010) Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension. Circulation 122:920-927
200. Speich R, Boehler A, Rochat T et al (2000) Cystic fibrosis: Current therapy. Indications for lung transplantation. Schweiz Med Wochenschr Suppl 122:57S-58S
201. Spence R, Mandagere A, Richards DB et al (2010) Potential for pharmacokinetic interactions between ambrisentan and cyclosporine. Clin Pharmacol Ther 88:513-520
202. Steen VD (2005) Autoantibodies in systemic sclerosis. Semin Arthritis Rheum 35:35-42
203. Steiner MK, Syrkina OL, Kolliputi N et al (2009) Interleukin-6 overexpression induces pulmonary hypertension. Circ Res 104:236-244, 228p following 244
204. Stojanovich L, Stojanovich R, Kostich V et al (2003) Neuropsychiatric lupus favourable response to low dose i.v. cyclophosphamide and prednisolone (pilot study). Lupus 12:3-7
205. Sutendra G, Dromparis P, Bonnet S et al (2011) Pyruvate dehydrogenase inhibition by the inflammatory cytokine TNFalpha contributes to the pathogenesis of pulmonary arterial hypertension. J Mol Med (Berl) 89:771-783
206. Suzuki C, Takahashi M, Morimoto H et al (2006) Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats. Biochem Biophys Res Commun 349:781-788
207. Sztrymf B, Souza R, Bertoletti L et al (2010) Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension. Eur Respir J 35:1286-1293
208. Tamby MC, Chanseaud Y, Humbert M et al (2005) Anti-endothelial cell antibodies in idiopathic and systemic sclerosis associated pulmonary arterial hypertension. Thorax 60:765-772
209. Tamby MC, Humbert M, Guilpain P et al (2006) Antibodies to fibroblasts in idiopathic and scleroderma-associated pulmonary hypertension. Eur Respir J 28:799-807
210. Tamosiuniene R, Tian W, Dhillon G et al (2011) Regulatory T cells limit vascular endothelial injury and prevent pulmonary hypertension. Circ Res 109:867-879
211. Tanaka E, Harigai M, Tanaka M et al (2002) Pulmonary hypertension in systemic lupus erythematosus: Evaluation of clinical characteristics and response to immunosuppressive treatment. J Rheumatol 29:282-287
212. Taraseviciene-Stewart L, Nicolls MR, Kraskauskas D et al (2007) Absence of T cells confers increased pulmonary arterial hypertension and vascular remodeling. Am J Respir Crit Care Med 175:1280-1289
213. Tashkin DP, Elashoff R, Clements PJ et al (2006) Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 354:2655-2666
214. Terrier B, Tamby MC, Camoin L et al (2008) Identification of target antigens of antifibroblast antibodies in pulmonary arterial hypertension. Am J Respir Crit Care Med 177:1128-1134
215. Terrier B, Tamby MC, Camoin L et al (2009) Antifibroblast antibodies from systemic sclerosis patients bind to {alpha}-enolase and are associated with interstitial lung disease. Ann Rheum Dis 69:428-433
216. Thurnheer R, Jenni R, Russi EW et al (1997) Hyperthyroidism and pulmonary hypertension. J Intern Med 242:185-188
217. Torbicki A, Kurzyna M, Kuca P et al (2003) Detectable serum cardiac troponin T as a marker of poor prognosis among patients with chronic precapillary pulmonary hypertension. Circulation 108:844-848
218. Torre O, Harari S (2011) Pleural and pulmonary involvement in systemic lupus erythematosus. Presse Med 40:e19-e29
219. Tsuda K, Yamanaka K, Kitagawa H et al (2012) Calcineurin inhibitors suppress cytokine production from memory T cells and differentiation of naive T cells into cytokine-producing mature T cells. PLoS One 7:e31465
220. Tuder RM (2009) Pathology of pulmonary arterial hypertension. Semin Respir Crit Care Med 30:376-385
221. Tuder RM, Groves B, Badesch DB et al (1994) Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am J Pathol 144:275-285
222. Tyndall AJ, Bannert B, VonkMet al (2010) Causes and risk factors for death in systemic sclerosis: A study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis 69:1809-1815
223. Ulrich S, Nicolls MR, Taraseviciene L et al (2008a) Increased regulatory and decreased CD8+ cytotoxic T cells in the blood of patients with idiopathic pulmonary arterial hypertension. Respiration 75:272-280
224. Ulrich S, Taraseviciene-Stewart L, Huber LC et al (2008b) Peripheral blood B lymphocytes derived from patients with idiopathic pulmonary arterial hypertension express a different RNA pattern compared with healthy controls: A cross sectional study. Respir Res 9:20
225. Vajner L, Vytasek R, Lachmanova V et al (2006) Acute and chronic hypoxia as well as 7-day recovery from chronic hypoxia affects the distribution of pulmonary mast cells and their MMP-13 expression in rats. Int J Exp Pathol 87:383-391
226. Valmary S, Dorfmuller P, Montani D et al (2011) Human gamma-herpesviruses Epstein-Barr virus and human herpesvirus-8 are not detected in the lungs of patients with severe pulmonary arterial hypertension. Chest 139:1310-1316
227. van den Hoogen FH, Boerbooms AM, Swaak AJ et al (1996) Comparison of methotrexate with placebo in the treatment of systemic sclerosis: A 24 week randomized double-blind trial, followed by a 24 week observational trial. Br J Rheumatol 35:364-372
228. Venitz J, Zack J, Gillies H et al (2012) Clinical pharmacokinetics and drug-drug interactions of endothelin receptor antagonists in pulmonary arterial hypertension. J Clin Pharmacol 52 (12):1784-1805
229. Wang W, Yan H, ZhuWet al (2009) Impairment of monocyte-derived dendritic cells in idiopathic pulmonary arterial hypertension. J Clin Immunol 29:705-713
230. Wang W, Wang YL, Chen XY et al (2011) Dexamethasone attenuates development of monocrotaline-induced pulmonary arterial hypertension. Mol Biol Rep 38:3277-3284
231. Yildirim-Toruner C, Diamond B (2011) Current and novel therapeutics in the treatment of systemic lupus erythematosus. J Allergy Clin Immunol 127:303-312, quiz 313-304
232. Zamora AC, Wolters PJ, Collard HR et al (2008) Use of mycophenolate mofetil to treat scleroderma-associated interstitial lung disease. Respir Med 102:150-155
233. Zheng Y, Li M, Zhang Y et al (2010) The effects and mechanisms of mycophenolate mofetil on pulmonary arterial hypertension in rats. Rheumatol Int 30:341-348
234. Zhou H (2005) Clinical pharmacokinetics of etanercept: A fully humanized soluble recombinant tumor necrosis factor receptor fusion protein. J Clin Pharmacol 45:490-497
235. Zitvogel L, Apetoh L, Ghiringhelli F et al (2008) The anticancer immune response: Indispensable for therapeutic success J Clin Invest 118:1991-2001