ASSOCIATIONS BETWEEN IL-13 AND IL-4 (MESSENGER-RNA AND PROTEIN), VASCULAR CELL-ADHESION MOLECULE-1 EXPRESSION, AND THE INFILTRATION OF EOSINOPHILS, MACROPHAGES, AND T-CELLS IN ALLERGEN-INDUCED LATE-PHASE CUTANEOUS REACTIONS IN ATOPIC SUBJECTS

IL-13, like IL-4, induces up-regulation of vascular cell adhesion mole cule-1 (VCAM-1) expression on human endothelial cells in vitro. This m ay contribute to local accumulation of alpha(4) beta(1)(+) inflammator y cells, such as eosinophils, macrophages, and T cells. We tested the hypothesis that in human allergic inflammatory reactions in vivo, IL-1 3 and IL-4 are both involved in VCAM-1/alpha(4) beta(1)-dependent recr uitment of inflammatory cells. Cryostat cutaneous sections from 13 ato pic subjects taken 6, 24, and 48 h after allergen challenge were proce ssed for immunohistochemical staining and in situ hybridization using mAbs and S-35-labeled riboprobes for IL-4 and IL-13. When compared wit h diluent sites, allergen provoked significant increases in the number s of cells that were mRNA(+) and protein-positive for both IL-13 and I L-4 that were clearly demonstrable at 6 h, peaked at 24 h, and decline d by 48 h. Double immunohistochemical staining/in situ hybridization s howed that the majority (>60%) of IL-13 mRNA(+) signals were colocaliz ed to CD3(+) T cells. The numbers of mRNA(+) and protein-positive cell s for IL-13 significantly correlated with VCAM-1 immunoreactivity on e ndothelial cells and with total numbers of infiltrating EG2(+) eosinop hils, CD45RO(+) T cells, and CD68(+) macrophages, but not elastase-pos itive neutrophils, at the 6- and 24-h time points. At 6 h, an associat ion was also observed between the numbers of IL-4 mRNA(+) or protein p roduct-positive cells and VCAM-1 expression, although this was not sta tistically significant. These findings suggest that IL-13 may play an important role in recruitment of inflammatory cells to the site of cut aneous allergic inflammatory reaction through VCAM-1 alpha(4) beta(1)- dependent, mechanisms.