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Preventive and remedial application of etanercept attenuate monocrotaline‐induced pulmonary arterial hypertension
Author(s) -
Zhang Lingling,
Lu Jie,
Li Mengtao,
Wang Qian,
Zeng Xiaofeng
Publication year - 2016
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.12304
Subject(s) - medicine , etanercept , pulmonary hypertension , cardiology , intensive care medicine , pharmacology , tumor necrosis factor alpha
Aim To evaluate the efficacy of etanercept ( ETN ) on monocrotaline ( MCT )‐induced pulmonary arterial hypertension ( PAH ) in rats. Methods A PAH rat model was induced by intraperitoneal injection (i.p.) of MCT (60 mg/kg) once and ENT therapy (2.5 mg/kg twice a week i.p.) was initiated on the day following MCT injection (prevention protocol) or after PAH is established (remedial protocol) for 2 weeks. The mean pulmonary arterial pressure (m PAP ) was measured using a right heart catheterization technique; quantitative determination of lung small artery blood wall thickening observed by hematoxylin and eosin staining; the expression of tumor necrosis factor ( TNF )‐α and interleukin (IL)‐6 in the rat lung tissues were determined using immunohistochemistry. Results Both preventive (12.53 ± 3.8 vs . model control 28.67 ± 7.57 mmHg, P < 0.01) and remedial (35.95 ± 20.29 vs . model control 66.17 ± 24.29 mmHg, P < 0.01) applications of ETN could significantly reduce mPAP . We obtained similar results when using the R ‐value to assess the efficacy of ETN in two treatment groups (preventive groups, 0.273 ± 0.018 vs . 0.203 ± 0.036, P < 0.01; remedial groups, 0.227 ± 0.031 vs . 0.124 ± 0.008, P < 0.01). The immunohistochemistry staining showed that there were strong expressions of TNF‐α and IL‐6 in the lung tissues of model groups and decreased expression in both treatment groups. Conclusion Treatment with TNF ‐α antagonism ETN prevented and reversed MCT ‐induced PAH by reducing inflammatory cell infiltration. Our results suggest a critical role of TNF ‐α and inflammation in MCT ‐induced PAH progression and targeting the inflammatory environment might be a potential means of PAH treatment.