ACTIVATION STATE OF POLYMORPHONUCLEAR NEU TROPHILS IN PATIENTS WITH ADULT-RESPIRATORY-DISTRESS-SYNDROME - ROLE OF CYTOKINE PRODUCTION

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.