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

Background: 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).

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.