S. Cholletmartin et al., ACTIVATION STATE OF POLYMORPHONUCLEAR NEU TROPHILS IN PATIENTS WITH ADULT-RESPIRATORY-DISTRESS-SYNDROME - ROLE OF CYTOKINE PRODUCTION, Pathologie et biologie, 41(8BIS), 1993, pp. 833-837
To gain further insight into the pathogenesis of the adult respiratory
distress syndrome (ARDS), the authors studied possible relationships
among the activation status of circulating polymorphonuclear neutrophi
ls (PMN), cytokine levels, and the severity of lung injury in 31 patie
nts: 15 with ARDS, 9 with severe pneumonia uncomplicated by ARDS, and
7 mechanically ventilated patients with neither ARDS nor pneumonia. Ni
ne healthy subjects served as controls. Using flow cytometry, the auth
ors identified a subpopulation of PMN with an increased capacity to ge
nerate hydrogen peroxide after stimulation ex vivo in all three patien
t groups ; significantly higher values were found in those with ARDS.
The PMN stimulation index, a reflection of the degree of hyperesponsiv
eness, correlated with elevated levels of tumor necrosis factor a (TNF
-alpha) in plasma, and both spontaneous and lipopolysaccharide (LPS)-i
nduced TNF-alpha production by cultured monocytes. These biological ex
pressions of PMN activation and cytokine generation both correlated wi
th indices of the severity of lung injury, but not with the overall cl
inical severity. In contrast, IL-6 and IL-1 beta showed little or no r
elationship with either the degree of lung injury or PMN hyperresponsi
veness. We conclude that TNFalpha-primed PMN may play a major role in
the pathogenesis of ARDS-associated lung injury.