Heart and Vessels

, Volume 25, Issue 5, pp 444–447 | Cite as

The efficacy of tocilizumab in a patient with pulmonary arterial hypertension associated with Castleman’s disease

  • Yoh Arita
  • Yasushi Sakata
  • Takao Sudo
  • Tetsuo Maeda
  • Ken Matsuoka
  • Keito Tamai
  • Kaori Higuchi
  • Wataru Shioyama
  • Yoshikazu Nakaoka
  • Yuzuru Kanakura
  • Keiko Yamauchi-Takihara
Case Report

Abstract

Castleman’s disease is a highly heterogeneous clinical-pathological entity that belongs to the lymphoproliferative disorders and is associated with pulmonary arterial hypertension (PAH) in some patients. It is linked to excessive immune stimulation by interleukin-6 (IL-6), which is also involved in the pathogenesis of PAH. A 31-year-old woman with Castleman’s disease demonstrated PAH characterized by severe right heart failure. Since she was resistant to various conventional therapies including steroids, prostacyclins, bosentan, and sildenafil, tocilizumab (anti-IL-6 receptor antibody) therapy was started. Her clinical course was followed for 6 months, with significant improvement without any adverse effect. This is the first reported case of use of tocilizumab in addition to steroids and conventional PAH therapy in a patient with PAH associated with Castleman’s disease.

Key words

Pulmonary arterial hypertension Interleukin-6 Cytokine Interleukin-6 receptor 

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References

  1. 1.
    Herrada J, Cabanillas F, Rice L, Manning J, Pugh W (1998) The clinical behavior of localized and multicentric Castleman disease. Ann Intern Med 128:657–662PubMedGoogle Scholar
  2. 2.
    Peterson BA, Frizzera G (1993) Multicentric Castleman’s disease. Semin Oncol 20:636–647PubMedGoogle Scholar
  3. 3.
    Yoshizaki K, Matsuda T, Nishimoto N, Kuritani T, Taeho L, Aozasa K, Nakahata T, Kawai H, Tagoh H, Komori T, Kishimoto S, Hirano T, Kishimoto T (1989) Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease. Blood 74:1360–1367PubMedGoogle Scholar
  4. 4.
    Oka H, Ikeda S, Koga S, Miyahara Y, Kohno S (2008) Atorvastatin induces associated reductions in platelet P-selectin, oxidized low-density lipoprotein, and interleukin-6 in patients with coronary artery diseases Heart Vessels 23:249–256CrossRefPubMedGoogle Scholar
  5. 5.
    Nishimoto N, Kanakura Y, Aozasa K, Johkoh T, Nakamura M, Nakano S, Nakano N, Ikeda Y, Sasaki T, Nishioka K, Hara M, Taguchi H, Kimura Y, Kato Y, Asaoku M, Kumagai S, Kodama F, Nakahara H, Hagihara K, Yoshizaki K, Kishimoto T (2005) Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. Blood 106:2627–2632CrossRefPubMedGoogle Scholar
  6. 6.
    Nishimoto N, Nakahara H, Yoshio-Hoshino N, Mima T (2008) Successful treatment of a patient with Takayasu arteritis using a humanized anti-interleukin-6 receptor antibody. Arthritis Rheum 58:1197–1200CrossRefPubMedGoogle Scholar
  7. 7.
    Nishimoto N, Yoshizaki K, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Hashimoto J, Azuma J, Kishimoto T (2004) Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 50:1761–1769CrossRefPubMedGoogle Scholar
  8. 8.
    Xiaohui L, Junbao D, Hongfang J, Bin G, Chaoshu T (2008) Sodium hydrosulfide alleviates pulmonary artery collagen remodeling in rats with high pulmonary blood flow. Heart Vessels 23:409–419CrossRefGoogle Scholar
  9. 9.
    Simonneau G, Galie N, Rubin LJ, Langleben D, Seeger W, Domenighetti G, Gibbs S, Lebrec D, Speich R, Beghettei M, Rich S, Fishman A (2004) Clinical classification of pulmonary hypertension. J Am Coll Cardiol 43suppl 12:5S–12SCrossRefPubMedGoogle Scholar
  10. 10.
    Bull TM, Cool CD, Seris AE, Rai PR, Parr J, Neid JM, Geraci MW, Campbell TB, Voelkel NF, Badesch DB (2003) Primary pulmonary hypertension, Castleman’s disease and human harpesvirus-8. Eur Respir J 22:403–407CrossRefPubMedGoogle Scholar
  11. 11.
    Montani D, Achouh L, Marcelin AG, Viard J-P, Hermine O, Canioni D, Sitbon O, Simonneau G, Humbert M (2005) Reversibility of pulmonary arterial hypertension in HIV/HHV8-associated Castleman’s disease. Eur Respir J 26:969–972CrossRefPubMedGoogle Scholar
  12. 12.
    American Thoracic Society (2002) ATS statement guidelines for the six-minute walk test. Am J Respir Crit Care Med 166:111–117Google Scholar
  13. 13.
    Beck JT, Hsu SM, Wijdenes J, Bataille R, Klein B, Vesole D, Hayden K, Jagannath S, Barlogie B (1994) Alleviation of systemic manifestations of Castleman’s disease by monoclonal anti-interleukin-6 antibody. N Engl J Med 330:602–605CrossRefPubMedGoogle Scholar
  14. 14.
    Nishimoto N, Sasai M, Shima Y, Nakagawa M, Matsumoto T, Shirai T, Kishimoto T, Yoshizaki K (2000) Improvement in Castleman’s disease by humanized anti-interleukin-6 antibody therapy. Blood 95:56–61PubMedGoogle Scholar
  15. 15.
    Humbert M, Monti G, Brenot F, Sitbon O, Portier A, Grangeot-Keros L, Duroux P, Galanaud P, Simonneau G, Emilie D (1995) Increased interleukin-1 and interleukin-6 serum concentration in severe primary pulmonary hypertension. Am J Respir Crit Care Med 151:1628–1631PubMedGoogle Scholar
  16. 16.
    Steiner MK, Syrkina OL, Kolliputi N, Mark EJ, Hales CA, Waxman AB (2009) Interleukin-6 overexpression induced pulmonary hypertension. Circ Res 104:236–244CrossRefPubMedGoogle Scholar
  17. 17.
    Ito T, Okada T, Miyashita H, Nomoto T, Nonaka-Sarukawa M, Uchibori R, Maeda Y, Urabe M, Mizukami H, Kume A, Takahashi M, Ikeda U, Shimada K, Ozawa K (2007) Interleukin-10 expression mediated by an adeno-associated virus vector prevents monocrotaline-induced pulmonary arterial hypertension in rats. Circ Res 101:734–741CrossRefPubMedGoogle Scholar
  18. 18.
    Nishimoto N, Terao K, Mima T, Nakahara H, Takagi N, Kakehi T (2008) Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood 112:3959–3964CrossRefPubMedGoogle Scholar
  19. 19.
    Nagaya N, Uematsu M, Satoh T, Kyotani S, Sakamaki F, Nkanishi N, Yamagishi M, Kunieda T, Miyatake K (1999) Serum uric acid levels correlate with the severity and the mortality of primary pulmonary hypertension. Am J Respir Crit Care Med 160:487–492PubMedGoogle Scholar

Copyright information

© Springer Japan 2010

Authors and Affiliations

  • Yoh Arita
    • 1
  • Yasushi Sakata
    • 1
  • Takao Sudo
    • 2
  • Tetsuo Maeda
    • 2
  • Ken Matsuoka
    • 1
  • Keito Tamai
    • 1
  • Kaori Higuchi
    • 1
  • Wataru Shioyama
    • 1
  • Yoshikazu Nakaoka
    • 1
  • Yuzuru Kanakura
    • 2
  • Keiko Yamauchi-Takihara
    • 1
  1. 1.Department of Cardiovascular MedicineOsaka University Graduate School of MedicineSuita, OsakaJapan
  2. 2.Department of Hematology and OncologyOsaka University Graduate School of MedicineOsakaJapan

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