BRONCHOALVEOLAR LAVAGE NEUTROPHILIA IS ASSOCIATED WITH OBLITERATIVE BRONCHIOLITIS AFTER LUNG TRANSPLANTATION ROLE OF IL-8

Obliterative bronchiolitis (OB) is a devastating complication in lung transplantation. We postulated that the pathogenesis of OB is mediated , in part, by neutrophils. We serially collected bronchoalveolar lavag e (BAL) fluid from lung transplant recipients. Patients were divided i nto two groups depending on the presence or absence of OB, Samples fro m patients who never developed OB were further divided according to wh ether rejection was present. These samples were labeled healthy or rej ection. Samples from patients who developed OB were divided according to whether the sample was obtained before (future OB) or at the time o f diagnosis of OB (OB). The OB group, as compared with the healthy and rejection group, had significantly elevated neutrophil counts (3.9x10 (5)+/-1.8x10(5) vs 0.3x10(5)+/-0.07x10(5) and 0.4x10(5)+/-0.1x10(5), r espectively, p <0.01 for both) and levels of IL-8 (3131+/-1468 pg/ml v s 240+/-62 pg/ml and 172+/-47 pg/ml, p <0.01 for both). Furthermore, w e demonstrated immunolocalization of IL-8 associated with alpha smooth muscle actin-positive cells in the peribronchial region of OB. To con firm that the IL-8 present in BAL fluid from patients with OB was bioa ctive, we performed neutrophil chemotaxis experiments that showed that IL-8 accounted for a significant amount of the neutrophil chemotatic activity. We also found a trend toward higher levels of neutrophils an d IL-8 in BALs from the future OB as compared with the healthy group ( 7.1x10(4)+/-4.2x10(4) vs 3.4x10(4)+/-0.7x10(4) and 500+/-306 pg/ml vs 240+/-62 pg/ml). In conclusion, we have provided the novel observation that in lung transplant recipients with OB, neutrophilia is present a nd highly correlated with the presence of IL-8.