INTERLEUKIN 8* (IL-S) IN THE BRONCHOALVEOLAR LAVAGE FLUID FROM PATIENTS WITH THE ADULT RESPIRATORY DISTRESS SYNDROME (ARDS) AND PATIENTS AT RISK FOR ARDS Philippe G. Jorens,2 Jo Van Damme, Wilfried De Backer,3 Leo Bossaert,z Rafael F. De Jongh,2 Arnold G. Herman,1 Marc Rampart’? A sensitive and specific radioimmunoassay was used to measure interleukin 8 (IL-g) in bronchoalveolar lavage fluids from control subjects, patients with the adult respiratory distress syndrome (ARDS) and patients undergoing coronary bypass surgery, a risk factor for developing ARDS. Concentrations of IL-8, albumin, total protein and numbers of neutrophils were higher in both patient groups than in controls. Levels of IL-8 were significantly correlated with the influx of neutrophils, plasma protein extravasation and with the Pa02/Fi0, ratio. These data suggest that IL-8 may mediate the recruitment of neutrophils from the vascular compartment into the alveolar space and may therefore be an important determinant in neutrophil-mediated lung injury. Since increased levels of IL-8 were also found in BAL fluid from patients at risk in whom ARDS did not develop, other factors are likely to be involved and IL-8, as well as other markers of inflammation, are of little prognostic use. Interleukin 8 (IL-g) is a 6.5 kDa cytokinel which belongs to a supergene family of host defense mol- ecules characterized by potent neutrophil-activating properties in vitro.2,3 In animal experiments, intra- dermal injection of picomolar amounts of IL-8 induces neutrophil emigration and neutrophil- dependent plasma protein extravasation.4 IL-8 can From the Divisions of lPharmacology, %tensive Care Medicine and 3Respiratory Medicine, University of Antwerp (UIA), and 4Rega Institute for Medical Research, University of Leuven, Belgium. Correspondence to: P. G. Jorens, Faculty of Medicine, Univer- sity of Antwerp (UIA), Universiteitsplein 1, B-2610 Wilrijk, Belgium. Marc Rampart and Jo Van Damme are Research Associates of the Belgian National Fund for Scientific Research. *Interleukin 8 has also been referred to as: neutrophil-activating peptide/protein 1 (NAP-l); neutrophil-activating factor (NAF); monocyte-derived neutrophil chemotactic factor/activating peptide (MDNCF, MONAP); granulocyte chemotactic pro- tein (GCP) and lymhocyte-derived neutrophil-activating peptide (LYNAP) TDeceased. Received 15 May 1992; revised and accepted for publication 27 July 1992 @ 1992 Academic Press Limited 1043-4666/921060592+06 $08.00/O KEY WORDS: adult respiratory distress syndrome (ARDS)/cardiopulmonary bypassiinterleukin 8 (IL- 8)/neutrophils(s)/pulmonary oedema 592 be produced by several cell types in vitro including macrophages, lymphocytes, neutrophils, fibroblasts and endothelial cells in response to a variety of stimuli such as endotoxin, virus and other cytokines such as interleukin 1 and tumour necrosis factor.2,3,5 In view of these observations, IL-8 has been impli- cated in a wide variety of pathological conditions characterized by neutrophil infiltration.2 So far IL-8 has been demonstrated in psoriatic scales,6 synovial fluids from patients with rheumatoid arthritis7,s and bronchoalveolar lavage fluid from patients with pul- monary fibrosis.9 The adult respiratory distress syndrome (ARDS) is an acute lung injury usually secondary to one or more major predisposing conditions such as sepsis, trauma and extracorporeal circulation.lOJl In the early stages, ARDS is characterized by neutrophil infiltration into the pulmonary interstitial and alveolar spaces,12 by non-cardiac high permeability oedema with leakage of plasma proteins into the alveoli and by refractory hypoxaemia.ll-l3 The pathogenesis of ARDS is largely unknown and the mortality remains well in excess of 50%.11 Although cases of ARDS have been reported in neutropenic patients,14 there is compelling clinical and experimental evidence that supports a central role for the neutrophil in the pathogenesis of ARDS. 12,13,15 Emigration of CYTOKINE, Vol. 4, No. 6 (November), 1992: pp 592-597