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Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease

Abstract

Selective skewing of autoreactive interferon-γ (IFN-γ)-producing T helper cells (Th1) toward an interleukin-4 (IL-4)-producing (Th2) phenotype can in experimental animals alleviate autoimmune disease without inducing general immunosuppression. In a prospective dose escalation study, we assessed treatment with human IL-4 (rhuIL-4) in 20 patients with severe psoriasis. The therapy was well tolerated, and within six weeks all patients showed decreased clinical scores and 15 improved more than 68%. Stable reduction of clinical scores was significantly better at 0.2–0.5 μg rhuIL-4 than at ≤0.1 μg rhuIL-4 (P = 0.009). In psoriatic lesions, treatment with 0.2–0.5 μg/kg rhuIL-4 reduced the concentrations of IL-8 and IL-19, two cytokines directly involved in psoriasis; the number of chemokine receptor CCR5+ Th1 cells; and the IFN-γ/IL-4 ratio. In the circulation, 0.2–0.5 μg/kg rhuIL-4 increased the number of IL-4+CD4+ T cells two- to three-fold. Thus, IL-4 therapy can induce Th2 differentiation in human CD4+ T cells and has promise as a potential treatment for psoriasis, a prototypic Th1-associated autoimmune disease.

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Figure 1: Enrichment of CCR5-expressing Th1 cells in psoriatic lesions.
Figure 2: Decrease of PASI during IL-4 therapy.
Figure 3: Decrease in skin thickness during IL-4 therapy.
Figure 4: Intralesional induction of Th2 responses and reduction of Th1 responses during IL-4 therapy.
Figure 5: Changes induced in the blood during therapy with rhuIL-4.

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Acknowledgements

We thank E.M. Shevach, Maryland; A.D. Levine, Ohio; and G. Riethmüller, Munich for helpful discussions and critical reading of the manuscript. We appreciate the excellent technical support by S. Barnsdorf, D. Dick, R. Gläser, S. Harrasser, D. Jakob, S. Multhaup, C. Reitmeier and B. Summer. This work was supported by the Deutsche Forschungsgemeinschaft RO 764/8-1, SFB 217 and 456, Wilhelm Sander-Stiftung (97.041.2) and the Schering-Plough Research Institute.

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Correspondence to Martin Röcken.

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The study described in this article was supported in part by Schering-Plough, which provided interleukin-4 and a portion of the costs of the study.

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Ghoreschi, K., Thomas, P., Breit, S. et al. Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease. Nat Med 9, 40–46 (2003). https://doi.org/10.1038/nm804

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