title: Preventive and remedial application of etanercept attenuate monocrotaline-induced pulmonary arterial hypertension.
abstract: OBJECTIVE
  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 (mPAP) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Meng-Tao
authors.initials: MT
authors.lastname: Li
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zeng
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D000068800:Etanercept / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016686:Monocrotaline; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D066253:Vascular Remodeling / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016686:Monocrotaline; D000068800:Etanercept
keywords: ETN; PAH; TNF-α; preventive; remedial