Interleukin-8 and neutrophils in systemic sclerosis with lung involvement.
We investigated the mechanisms and consequences of neutrophil accumulation in the airspace in 11 patients with systemic sclerosis (SSc) and interstitial lung disease. Seven normal subjects served as controls. We measured total neutrophil elastase burden, elastase activity, and alpha-1-antitrypsin (alpha 1AT) in bronchoalveolar lavage (BAL) fluid and we evaluated the in vitro interleukin-8 (IL-8, a potent chemoattractant for neutrophils) secretion by alveolar macrophages (AM). A mild neutrophil alveolitis was observed in patients when compared with control subjects. Total BAL elastase burden was higher in patients than in control subjects and correlated positively with the percentage of neutrophils in BAL. BAL elastase activity was undetectable in control subjects, but it was detected in all patients but one (mean: 257 +/- 87 mU/L). Spontaneous IL-8 secretion by AM was higher in patients with SSc than in control subjects (518 +/- 115 versus 228 +/- 65 ng/ml, p = 0.04) and positively correlated with the percentage of neutrophils in BAL (r = 0.505). We conclude that (1) the neutrophil could participate in the pathogenesis of SSC lung disease through the release of elastase; (2) the AM could contribute to the influx of neutrophils in the alveolus through the release of IL-8.
Unité INSERM 408, Hôpital Bichat, Paris, France.
B
B
Crestani
N
N
Seta
E
E
Palazzo
C
C
Rolland
P
P
Venembre
M
M
Dehoux
A
A
Boutten
P
P
Soler
M C
MC
Dombret
M F
MF
Kahn
D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000032:analysis*; D007958:Leukocyte Count; D019272:Leukocyte Elastase; D008070:Lipopolysaccharides / Q000494:pharmacology; D017563:Lung Diseases, Interstitial / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*; D010196:Pancreatic Elastase / Q000032:analysis; D012595:Scleroderma, Systemic / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D000515:alpha 1-Antitrypsin / Q000032:analysis
D016209:Interleukin-8; D008070:Lipopolysaccharides; D000515:alpha 1-Antitrypsin; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase