A molecule solves psoriasis? Systemic therapies for psoriasis inducing interleukin 4 and Th2 responses.
Psoriasis is an autoimmune disease affecting 2-4% of the Caucasian population. Inflammatory processes induce the migration of interferon (IFN) gamma 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-gamma promote intracellular IFN-gamma production by activating signal transducer and activator of transcription (STAT) 4 or 1. STAT1 activation by IFN-gamma 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.
Ghoreschi
Kamran
K
Department of Dermatology, University of Tübingen, Liebermeisterstrasse 25, 72076 Tübingen, Germany.
Mrowietz
Ulrich
U
Röcken
Martin
M
D002762:Cholecalciferol / Q000031:analogs & derivatives / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis / Q000627:therapeutic use; D005650:Fumarates / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology; D015847:Interleukin-4 / Q000502:physiology* / Q000627:therapeutic use*; D008727:Methotrexate / Q000494:pharmacology / Q000627:therapeutic use; D010789:Phototherapy / Q000379:methods; D011565:Psoriasis / Q000188:drug therapy* / Q000503:physiopathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014801:Vitamin A / Q000494:pharmacology / Q000627:therapeutic use
D016207:Cytokines; D005650:Fumarates; D018836:Inflammation Mediators; D014801:Vitamin A; D002762:Cholecalciferol; D015847:Interleukin-4; C035088:diethyl fumarate; D016572:Cyclosporine; D008727:Methotrexate