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

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 S-35-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 macrophages (P = .0014) in patients with CIU compared with numbers in nonatopic control subjects. There A ere 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 immuno pathology 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.