title: Praziquantel reverses pulmonary hypertension and vascular remodeling in murine schistosomiasis.
abstract: BACKGROUND
  Schistosomiasis is the most common worldwide cause of pulmonary arterial hypertension. The anti-schistosome drug praziquantel has been shown to reverse the liver fibrosis associated with Schistosoma mansoni in mice.
  
  
  OBJECTIVE
  We sought to determine whether praziquantel reverses established pulmonary vascular remodeling and pulmonary hypertension in a mouse model of S. mansoni.
  
  
  METHODS
  Mice were infected percutaneously with S. mansoni. At 17 weeks after infection mice were either killed or received two doses of praziquantel or vehicle by oral gavage. Treated mice were studied at 25 weeks after infection.
  
  
  RESULTS
  Vehicle-treated mice demonstrated significant increases in right ventricular systolic pressures (RVSP) and right ventricular hypertrophy (RVH) at 25 weeks, accompanied by pulmonary vascular remodeling. The degree of vascular remodeling correlated with proximity to granulomas. The elevation of RVSP and RVH at 25 weeks was dependent on the presence of eggs in the lung. Praziquantel eliminated the production of eggs in feces and led to clearance of eggs from the lung and to a lesser extent from liver. Praziquantel prevented the rise in RVSP and RVH seen in vehicle-treated mice and reversed established pulmonary vascular remodeling. Praziquantel significantly reduced lung mRNA expression of IL-13, IL-8, and IL-4, but did not reduce serum cytokine levels.
  
  
  CONCLUSIONS
  The development of pulmonary hypertension associated with S. mansoni infection can be prevented by praziquantel, and established vascular remodeling can be reversed. The mechanism involves clearance of lung eggs and reduced local expression of lung cytokines.
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, United Kingdom.
authors.forename: Alexi
authors.initials: A
authors.lastname: Crosby
authors.forename: Frances M
authors.initials: FM
authors.lastname: Jones
authors.forename: Ewa
authors.initials: E
authors.lastname: Kolosionek
authors.forename: Mark
authors.initials: M
authors.lastname: Southwood
authors.forename: Ian
authors.initials: I
authors.lastname: Purvis
authors.forename: Elaine
authors.initials: E
authors.lastname: Soon
authors.forename: Ghazwan
authors.initials: G
authors.lastname: Butrous
authors.forename: David E
authors.initials: DE
authors.lastname: Dunne
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Morrell
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001794:Blood Pressure; D001808:Blood Vessels / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006099:Granuloma / Q000469:parasitology / Q000473:pathology; D006352:Heart Ventricles / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000469:parasitology / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000469:parasitology / Q000503:physiopathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008099:Liver / Q000469:parasitology; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D010063:Ovum / Q000187:drug effects; D011223:Praziquantel / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D012550:Schistosoma mansoni / Q000187:drug effects; D012555:Schistosomiasis mansoni / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000871:Anthelmintics; D016207:Cytokines; D018836:Inflammation Mediators; D018793:Interleukin-13; D016209:Interleukin-8; D012333:RNA, Messenger; D015847:Interleukin-4; D011223:Praziquantel