ROLE OF INTERLEUKIN-4 AND VASCULAR CELL-ADHESION MOLECULE-1 IN SELECTIVE EOSINOPHIL MIGRATION INTO THE AIRWAYS IN ALLERGIC-ASTHMA

Recent in vitro studies have suggested that interleukin-4 (IL-4) may b e involved in the preferential migration of eosinophils into the airwa ys in allergic asthma through its capacity to selectively increase vas cular cell adhesion molecule-1 (VCAM-1) expression on vessels. To test this hypothesis, we studied the expression of VCAM-1, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) on vascular endothelium in bronchial mucosal biopsies from 20 allergic asthmatics using an immun ohistochemistry technique and related the observations to IL-4 levels in bronchoalveolar lavage (BAL) fluid simultaneously obtained and to e osinophil infiltration in the bronchial mucosa. IL-4 was detectable in BAL fluid from nine subjects (range, 15.1 to 110 pg/ml in 20-fold con centrated BAL fluid) (IL-4-positive asthmatics) but unmeasurable in th e remaining 11 subjects (IL-4-negative asthmatics). The IL-4-positive asthmatics showed a significantly increased expression of VCAM-1 but n ot E-selectin and ICAM-1 on vessels as compared with both IL-4-negativ e asthmatics (P < 0.001) and diseased control subjects (P < 0.001). In asthmatics, VCAM-1 expression was positively correlated with BAL IL-4 levels (r(s) = 0.89; P < 0.0001). Moreover, there was a significant c orrelation between the endothelial expression of VCAM-1 and the number of eosinophils, but not neutrophils, in the bronchial submucosa (r(2) = 0.76; P < 0.001). A significant correlation was also found between BAL IL-4 levels and the number of eosinophils. These results suggest t hat IL-4 is a VCAM-1-selective activator also in human airways and the VCAM-1-dependent pathways play a role in selective migration of eosin ophils into the airways in allergic asthma, and support the hypothesis described above.