BACKGROUND: Fumarates have been shown to be effective in psoriasis vulgaris. OBJECTIVES: To find out whether successful therapy is associated with modulation of cytokines. METHODS: We determined interferon (IFN)-gamma, interleukin (IL)-4 and IL-10 secretion capacities of peripheral blood mononuclear cells (PBMC) after phytohaemagglutinin stimulation, and IL-12p70 and IL-10 secretion capacities of PBMC after endotoxin stimulation in psoriasis vulgaris patients during treatment with fumarates. In a cohort study, 12 patients (five men, median age 50 years; seven women, median age 46 years) with psoriasis vulgaris were followed during 24 months of fumarate treatment. In addition, we followed 14 healthy controls (six men, median age 31 years; eight women, median age 29 years) without skin diseases during 12 months to investigate possible changes in the cytokine secretion capacity of PBMC as a result of seasonal changes. Disease activity in patients was determined by Psoriasis Area and Severity Index (PASI) score. Blood was collected for measurement by enzyme-linked immunosorbent assay of cytokine levels after stimulation of PBMC. RESULTS: Within 6 months of fumarate treatment, the mean +/- SD PASI score had decreased to 22 +/- 9% of its initial value. These beneficial effects coincided with lymphocytopenia and a significant (P < 0.05) downregulation of IFN-gamma expression by circulating blood cells, followed by a significant downregulation of IL-4 expression. Notably, production of the cytokine synthesis inhibitor IL-10 by PBMC was unchanged. CONCLUSIONS: The beneficial effects of fumarates may be attributed to their downregulatory action on type 1 cytokines.
BACKGROUND: Fumarates have been shown to be effective in psoriasis vulgaris. OBJECTIVES: To find out whether successful therapy is associated with modulation of cytokines. METHODS: We determined interferon (IFN)-gamma, interleukin (IL)-4 and IL-10 secretion capacities of peripheral blood mononuclear cells (PBMC) after phytohaemagglutinin stimulation, and IL-12p70 and IL-10 secretion capacities of PBMC after endotoxin stimulation in psoriasis vulgarispatients during treatment with fumarates. In a cohort study, 12 patients (five men, median age 50 years; seven women, median age 46 years) with psoriasis vulgaris were followed during 24 months of fumarate treatment. In addition, we followed 14 healthy controls (six men, median age 31 years; eight women, median age 29 years) without skin diseases during 12 months to investigate possible changes in the cytokine secretion capacity of PBMC as a result of seasonal changes. Disease activity in patients was determined by Psoriasis Area and Severity Index (PASI) score. Blood was collected for measurement by enzyme-linked immunosorbent assay of cytokine levels after stimulation of PBMC. RESULTS: Within 6 months of fumarate treatment, the mean +/- SD PASI score had decreased to 22 +/- 9% of its initial value. These beneficial effects coincided with lymphocytopenia and a significant (P < 0.05) downregulation of IFN-gamma expression by circulating blood cells, followed by a significant downregulation of IL-4 expression. Notably, production of the cytokine synthesis inhibitor IL-10 by PBMC was unchanged. CONCLUSIONS: The beneficial effects of fumarates may be attributed to their downregulatory action on type 1 cytokines.
Authors: Nicolle H R Litjens; Jacobus Burggraaf; Elisabeth van Strijen; Co van Gulpen; Herman Mattie; Rik C Schoemaker; Jaap T van Dissel; H Bing Thio; Peter H Nibbering Journal: Br J Clin Pharmacol Date: 2004-10 Impact factor: 4.335
Authors: Kamran Ghoreschi; Jürgen Brück; Christina Kellerer; Caishu Deng; Haiyan Peng; Oliver Rothfuss; Rehana Z Hussain; Anne R Gocke; Annedore Respa; Ivana Glocova; Nadejda Valtcheva; Eva Alexander; Susanne Feil; Robert Feil; Klaus Schulze-Osthoff; Rudolf A Rupec; Amy E Lovett-Racke; Ralf Dringen; Michael K Racke; Martin Röcken Journal: J Exp Med Date: 2011-10-10 Impact factor: 14.307
Authors: A Nast; I Kopp; M Augustin; K B Banditt; W H Boehncke; M Follmann; M Friedrich; M Huber; C Kahl; J Klaus; J Koza; I Kreiselmaier; J Mohr; U Mrowietz; H M Ockenfels; H D Orzechowski; J Prinz; K Reich; T Rosenbach; S Rosumeck; M Schlaeger; G Schmid-Ott; M Sebastian; V Streit; T Weberschock; B Rzany Journal: Arch Dermatol Res Date: 2007-05-12 Impact factor: 3.017
Authors: Nicolle H R Litjens; Elisabeth van Strijen; Co van Gulpen; Herman Mattie; Jaap T van Dissel; H Bing Thio; Peter H Nibbering Journal: BMC Pharmacol Date: 2004-10-12