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Dexamethasone attenuates development of monocrotaline-induced pulmonary arterial hypertension

  • Wei Wang
  • Yu-lin WangEmail author
  • Xiao-ying Chen
  • Yu-tang Li
  • Wei Hao
  • You-peng Jin
  • Bo Han
Article

Abstract

Immunity and inflammation are well established factors in the pathogenesis of pulmonary arterial hypertension (PAH). We aimed to investigate whether dexamethasone (Dex), a potent immunosuppressant, could prevent the development of monocrotaline (MCT)-induced PAH in rats as compared with pyrrolidine dithiocarbamate (PDTC) and its effect on the immune mechanism. PAH in rats (n = 66) was induced by MCT (50 mg/kg) injected intraperitoneally. Two days after MCT treatment, Dex (1.0 mg/kg) and PDTC (100 mg/kg) were administered once daily for 21 days. Samples were collected at 7, 14, and 21 days. Dex effectively inhibited MCT-induced PAH and reduced the T-helper (Th) 1 dominant cytokine response (interferon-γ) but up-regulated the Th2 one (interleukin 4). It increased the number of CD4+ T cells and decreased the number of CD8+ T cells around pulmonary arteries, upregulated the mRNA expression of fractalkine and downregulated that of CX3CR1 in the lung. Serum levels of interferon γ and interleukin 4 did not significantly differ from that of controls. Dex attenuated the process of MCT-induced PAH through its immunomodulatory property. Dex could be an appropriate therapy for PAH, although more studies are needed to define the appropriate treatment regimen.

Keywords

Dexamethasone Monocrotaline T cell Immune response 

Notes

Acknowledgments

The authors are grateful to Fengqin Liu and Qingqing Wang for excellent secretarial work. We also greatly appreciate the staff of the Central Laboratory of our hospital.

Supplementary material

11033_2010_390_MOESM1_ESM.jpg (1.2 mb)
Fig. S1 Immunohistochemical analysis of macrophages in rat lungs. Sections were from control treatment (a), 1 week post-MCT treatment (b), 2 weeks post-MCT treatment (c), 3 weeks post-MCT treatment (d), PDTC treatment (e), Dex treatment (f). Positive-stained cells are brown. Magnification ×400 (JPEG 1227 kb)

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Wei Wang
    • 1
  • Yu-lin Wang
    • 1
    Email author
  • Xiao-ying Chen
    • 1
  • Yu-tang Li
    • 2
  • Wei Hao
    • 1
  • You-peng Jin
    • 1
  • Bo Han
    • 1
  1. 1.Department of Pediatrics, Shandong Provincial HospitalShandong UniversityJi’nanChina
  2. 2.Department of Immunology and Microbiology Laboratory, School of MedicineShandong UniversityJi’nanChina

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