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A molecule solves psoriasis? Systemic therapies for psoriasis inducing interleukin 4 and Th2 responses

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Abstract

Psoriasis is an autoimmune disease affecting 2–4% of the Caucasian population. Inflammatory processes induce the migration of interferon (IFN) γ producing Th1 lymphocytes into the skin. These play a key role in the pathogenesis of psoriasis. These Th1 lymphocytes are responsible for the pathological reactions in psoriatic skin leading to keratinocyte hyperproliferation, small vessel proliferation and neutrophilic infiltration. Antigen-presenting cells activate dermal CD4+ T lymphocytes, and various signals can support the polarization of Th1 responses. The main signal for Th1 development is interleukin (IL) 12. After binding to their receptors both IL-12 and IFN-γ promote intracellular IFN-γ production by activating signal transducer and activator of transcription (STAT) 4 or 1. STAT1 activation by IFN-γ is followed by T-bet activation, a master transcription factor for Th1 lymphocytes. In experimental models of Th1-mediated autoimmune diseases immune deviation of polarized autoreactive Th1 into anti-inflammatory Th2 responses generally improves the disease. Therefore new therapeutic approaches based on immunomodulating molecules have been developed for psoriasis, a prototypical Th1-mediated autoimmune disorder. Recently IL-4, the most effective Th2-inducing cytokine, has been shown to be safe and efficient for treating psoriasis. Improvement was associated with the induction of a Th2 phenotype of skin infiltrating lymphocytes. This review summarizes the IL-4 inducing potential of various conventional and newer systemic therapies for psoriasis. Many of these were thought to be primarily immunosuppressive. A review of the literature reveals that most of them can induce IL-4 and Th2, and that Th2 induction may be an underestimated mode of action in the therapy of Th1-mediated autoimmune disease. Further studies are needed to determine the central role of IL-4 in the control of Th1-induced autoimmune disease, namely psoriasis.

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Abbreviations

APC :

Antigen-presenting cells

DC :

Dendritic cells

EAE :

Autoimmune encephalomyelitis

FAE :

Fumaric acid ester

IFN :

Interferon

IL :

Interleukin

IκB :

Inhibitor protein of nuclear transcription factor κB

MHF :

Methylhydrogen fumarate

NF :

Nuclear factor

NFAT :

Nuclear factor of activated T cells

PASI :

Psoriasis Area and Severity Index

STAT :

Signal transducer and activator of transcription

Th :

T helper cell

TNF :

Tumor necrosis factor

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Authors and Affiliations

  1. Department of Dermatology, University of Tübingen, Liebermeisterstrasse 25, 72076, Tübingen, Germany

    Kamran Ghoreschi & Martin Röcken

  2. Department of Dermatology, Campus Kiel, University of Schleswig-Holstein, Kiel, Germany

    Ulrich Mrowietz

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  1. Kamran Ghoreschi
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  2. Ulrich Mrowietz
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  3. Martin Röcken
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Correspondence to Martin Röcken.

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Ghoreschi, K., Mrowietz, U. & Röcken, M. A molecule solves psoriasis? Systemic therapies for psoriasis inducing interleukin 4 and Th2 responses. J Mol Med 81, 471–480 (2003). https://doi.org/10.1007/s00109-003-0460-9

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  • DOI: https://doi.org/10.1007/s00109-003-0460-9

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