Food allergy, anaphylaxis, dermatology, and drug allergy
Enhanced expression levels of IL-31 correlate with IL-4 and IL-13 in atopic and allergic contact dermatitis

https://doi.org/10.1016/j.jaci.2006.07.015Get rights and content

Background

IL-31 is produced by activated T lymphocytes, preferentially by TH2 cells. Transgenic mice overexpressing IL-31 have a phenotype resembling allergic dermatitis in human subjects.

Objective

We sought to evaluate the potential importance of IL-31 in the pathogenesis of human T cell–mediated skin diseases.

Methods

We analyzed total RNA taken from 149 skin biopsy specimens from patients with atopic dermatitis (AD), allergic contact dermatitis (ACD), or psoriasis in comparison with specimens taken from patients with healthy skin (n = 13) by using quantitative real-time PCR for the expression of TH1/TH2 cytokines.

Results

We found statistically increased mRNA levels of IL-31 in biopsy specimens taken from patients with AD, irrespective of the severity of the disease and serum IgE levels. Moreover, IL-31 mRNA levels were strongly increased in many biopsy specimens taken from patients with ACD. However, no increased transcription of IL-31 could be detected in biopsy specimens taken from psoriatic plaques. A comparison of mRNA levels of IL-31 with TH1 or TH2 cytokines demonstrates a correlation of the expression of IL-31 with IL-4 and IL-13 but not with IFN-γ. No significant increase of IL-31 receptor mRNA could be detected in any disease, whereas the second receptor subunit of IL-31, the oncostatin M receptor, seems to be enhanced transcribed in patients with psoriasis.

Conclusion

IL-31 expression is not only increased in patients with AD but also in those with ACD, 2 pruritic skin disorders. In both types of eczema, expression of IL-31 is associated with the expression of the TH2 cytokines IL-4 and IL-13.

Clinical implications

IL-31 might contribute not only to the development of AD but also to ACD-provoked skin inflammation.

Section snippets

Patients

Punch biopsy specimens from lesional skin of patients with psoriasis (n = 60), AD (n = 33), or ACD (n = 56), as well as from control individuals without any history of atopic diseases (n = 13), were collected after obtaining informed consent in the Departments of Dermatology of the Universities of Aachen, Bonn, and Cologne, Germany, for Miltenyi Biotec GmbH as part of a study supported by the Technologie- und Innovationsprogramm NRW, Germany. In all cases the diagnosis was not only based on the

IL-31 expression in the skin of patients with AD does not correlate with serum IgE levels or severity of the disease

Quantitative real-time PCR analyses were performed of IL-31 mRNA in comparison with IL-4 and IL-13 (as classical TH2-type cytokines) and IFN-γ (as a TH1-type cytokine) to evaluate the role of IL-31 in the process of TH1/TH2-mediated inflammatory skin diseases.

AD is described as a biphasic inflammatory disease, in which antigen-specific activated T cells produce large amounts of TH2 cytokines (IL-4 and IL-13) shortly after manifestation. After 48 to 72 hours, however, the initial TH2 response

Discussion

IL-31 was recently identified as a novel 4-helix-bundle cytokine, and overexpression in transgenic mice led to a phenotype closely resembling AD in human patients.7 Analyzing 33 skin biopsy specimens taken from human AD lesions, we could demonstrate a statistically significant increase in IL-31 mRNA in comparison with that seen in healthy skin. This finding is in line with the recent publication by Sonkoly et al,21 in which the authors analyzed lesional and nonlesional skin of patients with AD,

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    Disclosure of potential conflict of interest: J. M. Baron, H. F. Merk, C. Mauch, T. Krieg, T. Bieber, J. Wenzel, and M. M. Neis have all received grant support from Forschungs-und Innovationsprogramm NRW. A. Bosio and B. Peters are both employed by Miltenyi Biotec. The rest of the authors have declared that they have no conflict of interest.

    Supported by the Technologie- und Innovationsprogramm NRW (to the dermatology departments of Aachen, Cologne, and Bonn and Miltenyi Biotec GmbH) and by the Deutsche Forschungsgemeinschaft (Bonn, Germany; SFB 542, TP C11 to H.F.M., J.M.B., and H.M.H.).

    These authors contributed equally to this work.

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