ROLE OF INTERLEUKIN-8 IN THE GENESIS OF ACUTE RESPIRATORY-DISTRESS SYNDROME THROUGH AN EFFECT ON NEUTROPHIL APOPTOSIS

Objective: To evaluate the role of interleukin 8 (IL-8) in the regulat ion of neutrophil (PMN) apoptosis in normal plasma and plasma from pat ients with early, fulminant acute respiratory distress syndrome (ARDS) . Design: Experimental study using cultured human PMNs. Setting: Unive rsity hospital, level I trauma center. Participants: Plasma was obtain ed from 6 patients with early, fulminant posttraumatic ARDS (mean Inju ry Severity Score, 26). All samples were drawn within 24 hours after i njury. Plasma was also taken from 13 healthy control subjects. These c ontrols were also used as sources of PMNs. Main Outcome Measures: Effe ct of early, Culminant ARDS and normal plasma on spontaneous apoptosis , CD16, and CD11-b expression in PMNs in vitro; levels of IL-8 in plas ma; correlation of extracellular IL-8 concentration with rate of PMN a poptosis; and effect of IL-8 blockade on PMN apoptosis, CD16, and CD11 -b expression in ARDS and normal plasma. Results: Plasma from patients with early, fulminant ARDS inhibited spontaneous PMN apoptosis at 24 hours (35% +/- 5% vs 54% +/- S%; P = .01). Neither CD16 nor CD11-b dif fered significantly between the 2 groups. The mean plasma level of IL- 8 in patients with early, fulminant ARDS was 359 +/- 161 pg/mL vs 3.0 +/- 0.4 pg/mL in healthy controls (P<.05). Interleukin 8 inhibited apo ptosis in plasma-free medium at low doses (1-50 pg/mL) but had no sign ificant effect at higher doses (100-5000 pg/mL) (P<.05). Interleukin 8 blockade with monoclonal antibody suppressed apoptosis in normal plas ma (28% +/- 5% with monoclonal antibody vs 51% +/- 5% without monoclon al antibody; P = .008) but not in plasma from patients with early, ful minant ARDS (29% +/- 5% with monoclonal antibody vs 34% +/- 6% without monoclonal. antibody; P = .67). It had no effect on CD16 or CD11-b ex pression in either plasma. Conclusions: Plasma from patients with earl y, fulminant ARDS contains soluble factors that inhibit PMN apoptosis in vitro. Low levels of IL-8 inhibit PMN apoptosis in normal plasma. A lthough plasma levels of IL-8 are markedly elevated in early, fulminan t ARDS, IL-8 is not directly responsible for the antiapoptotic effect of plasma from patients with early, fulminant ARDS.