title: Exaggerated TNFalpha release of alveolar macrophages in corticosteroid resistant sarcoidosis.
abstract: OBJECTIVE
  The aim of the present study was to determine the TNFalpha release of cultured alveolar macrophages (AM) and the bronchoalveolar lavage (BAL) cellular profile in 35 patients suffering from long lasting sarcoidosis.
  
  
  METHODS
  The AM TNFalpha release and the BAL cellular profile of 35 patients with a mean duration of sarcoidosis of 10.4 +/- 1.3 years at the time of BAL was compared to 35 healthy controls.
  
  
  RESULTS
  The BAL profile of 12 sarcoid patients with a stable disease was similar to that known from acute sarcoidosis. Sarcoid patients with progressive disease (n = 12) and sarcoid patients with corticosteroid resistant disease (n = 11) were characterised by a normal CD4/CD8 ratio and a significant increase of BAL neutrophils (2.7 +/- 1.0% and 3.8 +/- 1.1%, respectively). The AM TNFalpha release of sarcoid patients with stable disease did not differ significantly from controls (523 +/- 124 pg/ml vs. 410 +/- 104 pg/ml). In contrast, we observed a significantly elevated TNFalpha release in sarcoid patients with progressive (2,124 +/- 550 pg/ml; p < 0.01) as well as in those with a corticosteroid resistant disease (1,585 +/- 520 pg/ml; p < 0.01) compared to controls.
  
  
  CONCLUSIONS
  Chronic sarcoid patients in a progressive phase of the disease and those with a corticosteroid resistant disease are characterised by a significantly increased TNFalpha release of cultured AM. Our results support the usage of chimeric anti-TNFalpha antibodies as an alternative therapeutic regimen in chronic corticosteroid resistant sarcoidosis.
authors.affiliation: University Hospital Freiburg, Dep of Pneumology, Germany. ziegenhagen@med1.ukl.uni-freiburg.de
authors.forename: Manfred W
authors.initials: MW
authors.lastname: Ziegenhagen
authors.forename: Manuela E
authors.initials: ME
authors.lastname: Rothe
authors.forename: Gernot
authors.initials: G
authors.lastname: Zissel
authors.forename: Joachim
authors.initials: J
authors.lastname: Müller-Quernheim
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D002908:Chronic Disease; D018450:Disease Progression; D004351:Drug Resistance; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017565:Sarcoidosis, Pulmonary / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000502:physiology
chemical_list: D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha