title: Severe asthma is associated with a loss of LX4, an endogenous anti-inflammatory compound.
abstract: BACKGROUND
  Lipoxins and 15-epi-lipoxins are lipid mediators that modulate leukocyte trafficking and promote the inflammation resolution. They are produced by different enzymatic pathways. Patients with severe asthma present ongoing airway inflammation despite chronic long-term treatment including oral glucocorticoids.
  
  
  OBJECTIVE
  The aim of this study was to assess the presence of proinflammatory and anti-inflammatory mediators in the supernatants of induced sputum.
  
  
  METHODS
  Induced sputum supernatants were collected from 10 normal subjects; 12 subjects with mild, 15 with moderate, and 24 with severe asthma; and 13 patients with chronic obstructive pulmonary disease. First, we validated the measurements of IL-8, leukotriene B 4 , lipoxin A 4 , and 15-epi-lipoxin A 4 in these samples. Then we measured these mediators by using immunoenzymatic methods.
  
  
  RESULTS
  IL-8 levels were highly increased in patients with severe asthma ( P < .0001), and leukotriene B 4 levels were significantly increased in patients with severe asthma and patients with chronic obstructive pulmonary disease. Lipoxin A 4 was significantly increased in the supernatant obtained from patients with mild asthma ( P < .0001), whereas 15-epi-lipoxin A 4 levels were higher in patients with severe asthma ( P = .05). More interestingly, we found a positive correlation between the level of lipoxin A 4 and IL-8 in patients with mild asthma.
  
  
  CONCLUSIONS
  These results indicate that induced sputum is a suitable method to assess lipoxin and 15-epi-lipoxin measurements in bronchi. The mechanisms involved in the synthesis of these 2 eicosanoid mediators would be helpful to understand better the imbalance between proinflammatory and anti-inflammatory mediators occurring in severe asthma. Lipoxin production involves interaction between lipoxygenases, whereas 15-epi-lipoxin production might involve CytP450 activity.
authors.affiliation: Clinique des Maladies Respiratoires, CHU, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vachier
authors.forename: Caroline
authors.initials: C
authors.lastname: Bonnans
authors.forename: Claude
authors.initials: C
authors.lastname: Chavis
authors.forename: Martine
authors.initials: M
authors.lastname: Farce
authors.forename: Philippe
authors.initials: P
authors.lastname: Godard
authors.forename: Jean
authors.initials: J
authors.lastname: Bousquet
authors.forename: Pascal
authors.initials: P
authors.lastname: Chanez
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000032:analysis / Q000096:biosynthesis; D044045:Lipoxins / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000276:immunology; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology; D013183:Sputum / Q000166:cytology / Q000276:immunology*
chemical_list: D016209:Interleukin-8; D044045:Lipoxins; C040527:lipoxin A4; D007975:Leukotriene B4