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Paper
November 1998

Role of Interleukin 8 in the Genesis of Acute Respiratory Distress Syndrome Through an Effect on Neutrophil Apoptosis

Author Affiliations

From the Department of Surgery, University of Medicine and Dentistry of New Jersey[[ndash]]New Jersey Medical School, Newark.

Arch Surg. 1998;133(11):1234-1239. doi:10.1001/archsurg.133.11.1234
Abstract

Objective  To evaluate the role of interleukin 8 (IL-8) in the regulation of neutrophil (PMN) apoptosis in normal plasma and plasma from patients with early, fulminant acute respiratory distress syndrome (ARDS).

Design  Experimental study using cultured human PMNs.

Setting  University hospital, level I trauma center.

Participants  Plasma was obtained from 6 patients with early, fulminant posttraumatic ARDS (mean Injury Severity Score, 26). All samples were drawn within 24 hours after injury. Plasma was also taken from 13 healthy control subjects. These controls were also used as sources of PMNs.

Main Outcome Measures  Effect of early, fulminant ARDS and normal plasma on spontaneous apoptosis, CD16, and CD11-b expression in PMNs in vitro; levels of IL-8 in plasma; correlation of extracellular IL-8 concentration with rate of PMN apoptosis; 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%±5%; P=.01). Neither CD16 nor CD11-b differed 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 apoptosis in plasma-free medium at low doses (1-50 pg/mL) but had no significant effect at higher doses (100-5000 pg/mL) (P<.05). Interleukin 8 blockade with monoclonal antibody suppressed apoptosis in normal plasma (28%±5% with monoclonal antibody vs 51%±5% without monoclonal antibody; P=.008) but not in plasma from patients with early, fulminant ARDS (29%±5% with monoclonal antibody vs 34%±6% without monoclonal antibody; P=.67). It had no effect on CD16 or CD11-b expression in either plasma.

Conclusions  Plasma from patients with early, fulminant ARDS contains soluble factors that inhibit PMN apoptosis in vitro. Low levels of IL-8 inhibit PMN apoptosis in normal plasma. Although plasma levels of IL-8 are markedly elevated in early, fulminant ARDS, IL-8 is not directly responsible for the antiapoptotic effect of plasma from patients with early, fulminant ARDS.

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