Monocrotaline-induced pulmonary arterial hypertension is attenuated by TNF-α antagonists via the suppression of TNF-α expression and NF-κB pathway in rats

Inflammation is involved in various types of human pulmonary arterial hypertension (PAH), especially in PAH-associated connective tissue diseases. Although the pathogenesis of pulmonary hypertension has still remained largely unclear, TNF-α has been reported as a key pro-inflammatory cytokine in severe pulmonary hypertension and emphysema. The aim of this study was to investigate the effect of a TNF-α antagonist, recombinant TNF-α receptor II:IgG Fc fusion protein (rhTNFRFc), on the development of monocrotaline (MCT)-induced PAH in rats. Our results revealed that treatment of rhTNFRFc in these rats had favorable effects on mPAP levels, hemodynamics and pulmonary vascular remodeling, preventing PAH development at 3 weeks following MCT. Furthermore, rhTNFRFc treatment resulted in markedly reduced expression of TNF-α via the inhibition of NF-κB activity in rat lungs. These results demonstrated that rhTNFRFc attenuated the process of MCT-induced PAH through its anti-inflammatory property. Although further studies are needed to define the appropriate treatment regimen, our findings suggest that rhTNFRFc might provide therapeutic benefits for PAH patients.

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