Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease.
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.
Ghoreschi
Kamran
K
Department of Dermatology and Allergology, Ludwig-Maximilians University Munich, Munich, Germany.
Thomas
Peter
P
Breit
Susanne
S
Dugas
Martin
M
Mailhammer
Reinhard
R
van Eden
Willem
W
van der Zee
Ruurd
R
Biedermann
Tilo
T
Prinz
Jörg
J
Mack
Matthias
M
Mrowietz
Ulrich
U
Christophers
Enno
E
Schlöndorff
Detlef
D
Plewig
Gerd
G
Sander
Christian A
CA
Röcken
Martin
M
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
C421250:IL19 protein, human; D020382:Interleukin-18; D007378:Interleukins; D019713:Receptors, CCR5; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma