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 3weeks 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.