Role of interleukin-4 and vascular cell adhesion molecule-1 in selective eosinophil migration into the airways in allergic asthma

Am J Respir Cell Mol Biol. 1996 Jan;14(1):84-94. doi: 10.1165/ajrcmb.14.1.8534490.


Recent in vitro studies have suggested that interleukin-4 (IL-4) may be involved in the preferential migration of eosinophils into the airways in allergic asthma through its capacity to selectively increase vascular 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 immunohistochemistry technique and related the observations to IL-4 levels in bronchoalveolar lavage (BAL) fluid simultaneously obtained and to eosinophil 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 concentrated BAL fluid) (IL-4-positive asthmatics) but unmeasurable in the remaining 11 subjects (IL-4-negative asthmatics). The IL-4-positive asthmatics showed a significantly increased expression of VCAM-1 but not E-selectin and ICAM-1 on vessels as compared with both IL-4-negative asthmatics (P < 0.001) and diseased control subjects (P < 0.001). In asthmatics, VCAM-1 expression was positively correlated with BAL IL-4 levels (rs = 0.89; P < 0.0001). Moreover, there was a significant correlation between the endothelial expression of VCAM-1 and the number of eosinophils, but not neutrophils, in the bronchial submucosa (r2 = 0.76; P < 0.001). A significant correlation was also found between BAL IL-4 levels and the number of eosinophils. These results suggest that 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 eosinophils into the airways in allergic asthma, and support the hypothesis described above.

MeSH terms

  • Adult
  • Asthma / pathology*
  • Bronchi / metabolism
  • Bronchi / pathology
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cell Movement
  • E-Selectin / analysis
  • Endothelium, Vascular / metabolism
  • Eosinophils / physiology*
  • Female
  • Humans
  • Intercellular Adhesion Molecule-1 / analysis
  • Interleukin-4 / analysis
  • Interleukin-4 / physiology*
  • Male
  • Middle Aged
  • Mucous Membrane / metabolism
  • Mucous Membrane / pathology
  • Vascular Cell Adhesion Molecule-1 / analysis
  • Vascular Cell Adhesion Molecule-1 / physiology*


  • E-Selectin
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Interleukin-4