title: Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease.
abstract: Selective skewing of autoreactive interferon-gamma (IFN-gamma)-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 microg rhuIL-4 than at < or =0.1 microg rhuIL-4 (P = 0.009). In psoriatic lesions, treatment with 0.2-0.5 microg/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-gamma/IL-4 ratio. In the circulation, 0.2-0.5 microg/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.
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilians University Munich, Munich, Germany.
authors.forename: Kamran
authors.initials: K
authors.lastname: Ghoreschi
authors.forename: Peter
authors.initials: P
authors.lastname: Thomas
authors.forename: Susanne
authors.initials: S
authors.lastname: Breit
authors.forename: Martin
authors.initials: M
authors.lastname: Dugas
authors.forename: Reinhard
authors.initials: R
authors.lastname: Mailhammer
authors.forename: Willem
authors.initials: W
authors.lastname: van Eden
authors.forename: Ruurd
authors.initials: R
authors.lastname: van der Zee
authors.forename: Tilo
authors.initials: T
authors.lastname: Biedermann
authors.forename: Jörg
authors.initials: J
authors.lastname: Prinz
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mrowietz
authors.forename: Enno
authors.initials: E
authors.lastname: Christophers
authors.forename: Detlef
authors.initials: D
authors.lastname: Schlöndorff
authors.forename: Gerd
authors.initials: G
authors.lastname: Plewig
authors.forename: Christian A
authors.initials: CA
authors.lastname: Sander
authors.forename: Martin
authors.initials: M
authors.lastname: Röcken
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D015847:Interleukin-4 / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D007378:Interleukins; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D019713:Receptors, CCR5 / Q000378:metabolism; D012720:Severity of Illness Index; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: C421250:IL19 protein, human; D020382:Interleukin-18; D007378:Interleukins; D019713:Receptors, CCR5; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma