title: Systemic treatment with either cyclosporin A or methotrexate does not influence the T helper 1/T helper 2 balance in psoriatic patients.
abstract: Cyclosporin A and methotrexate are highly effective drugs in the treatment of psoriasis. It was hypothesized that these therapies might modulate T helper cell cytokine secretion patterns or T cell migration patterns. Flow cytometric determination of interferon-gamma (IFNgamma) and interleukin 4 (IL4) producing T helper cell frequencies, as well as of cutaneous lymphocyte associated antigen (CLA) expressing T cell frequencies was performed in patients suffering from severe psoriasis, before, during, and after a scheduled immunosuppressive regimen with either cyclosporin A or methotrexate. Both cyclosporin A and methotrexate treatment reduced the psoriasis area severity index score after 12 weeks of treatment. Cyclosporin A treatment reduced the frequencies of IL4-producing CD4(pos) T cells, without significantly affecting the T helper 1 to T helper 2 (Th1/Th2) balance but in conjunction with the decreasing number of peripheral blood eosinophil counts. In methotrexate-treated patients, the Th1/Th2 balance was unaffected. Cessation of both therapies resulted in increased numbers of IFNgamma- as well as IL4-producing CD4(pos) T cells as compared to before initiation of oral therapy. Methotrexate, but not cyclosporin A, treatment reduced the frequencies of circulating skin-homing CLA(pos) T cells. This effect was reversed by 4 weeks after withdrawal of methotrexate therapy. We conclude that (1) neither cyclosporin A nor methotrexate affects the balance between Th1 and Th2 cells; (2) exaggerated cytokine production by T helper cells after cessation of oral cyclosporin A or methotrexate drug treatment may contribute to the reappearance of psoriatic skin lesions; and (3) decrease of circulating skin-homing T cells may be responsible for part of the therapeutic effect of methotrexate in severe psoriasis.
authors.affiliation: Laboratory for Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands. r.j.rentenaar@amc.uva.nl
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Rentenaar
authors.forename: Vera M R
authors.initials: VM
authors.lastname: Heydendael
authors.forename: Frank N J
authors.initials: FN
authors.lastname: van Diepen
authors.forename: Menno A
authors.initials: MA
authors.lastname: de Rie
authors.forename: Ineke J M
authors.initials: IJ
authors.lastname: ten Berge
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D016572:Cyclosporine / Q000008:administration & dosage*; D016207:Cytokines / Q000032:analysis; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma; D016572:Cyclosporine; D008727:Methotrexate