TH1/TH2 cytokines and inflammatory cells in skin biopsy specimens from patients with chronic idiopathic urticaria: comparison with the allergen-induced late-phase cutaneous reaction.

Abstract

Previous studies have demonstrated infiltration of eosinophils, neutrophils, monocytes, and T cells in the skin of patients with chronic idiopathic urticaria (CIU), suggesting a possible T(H)2-type cytokine pathology analogous to the allergen-induced skin late-phase reaction (LPR). We sought to compare skin biopsy specimens from patients with CIU and the allergen-induced skin LPR for mRNA(+) cells for IL-4, IL-5, and IFN-gamma and inflammatory cell infiltration. Skin biopsy specimens were obtained from 13 patients with CIU (6 had positive results for FcepsilonRI autoantibodies), 6 nonatopic control subjects, and 6 atopic subjects (before and after cutaneous allergen challenge). Cryostat sections were processed for immunohistochemistry and in situ hybridization by using the (35)S-riboprobes. There were significant increases in the numbers of intradermal CD3(+) (P =.007), CD4(+) (P =.004), CD8(+) (P =.012), and CD25(+) (P =.018) T cells, as well as eosinophils (P =.02), neutrophils (P =.01), basophils (P =.004), and macro-phages (P =.0014) in patients with CIU compared with numbers in nonatopic control subjects. There were lower numbers of tryptase-positive mast cells (P =.048). In the epidermis of patients with CIU, but not in that of normal subjects or in allergen-challenged biopsy specimens, there were increased numbers of CD3(+) T cells (P =.039). The profile of inflammatory cell infiltration in the allergen-induced skin LPR was similar to that in patients with CIU. In patients with CIU there was a T(H)0 cytokine profile, with significant increases in IL-4 (P =.0029), IL-5 (P =.0025), and IFN-gamma (P =.037) mRNA(+) cells. As expected, in the skin LPR there was an increase in IL-4 (P =.0082) and IL-5 (P =.0051), but not IFN-gamma, mRNA(+) cells. There were no significant differences in either the numbers of inflammatory cells or the cytokine pattern between patients with and without autoantibody. The molecular immunopathology of CIU is that of an eosinophil and basophil cell-mediated hypersensitivity reaction. Thus it is similar to the allergic skin LPR but has a T(H)0 rather than a T(H)2 cytokine profile.