title: Beneficial effects of fumarate therapy in psoriasis vulgaris patients coincide with downregulation of type 1 cytokines.
abstract: BACKGROUND
  Fumarates have been shown to be effective in psoriasis vulgaris.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Infectious Diseases, C5-P, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors.forename: N H R
authors.initials: NH
authors.lastname: Litjens
authors.forename: P H
authors.initials: PH
authors.lastname: Nibbering
authors.forename: A J
authors.initials: AJ
authors.lastname: Barrois
authors.forename: T P L
authors.initials: TP
authors.lastname: Zomerdijk
authors.forename: A C
authors.initials: AC
authors.lastname: Van Den Oudenrijn
authors.forename: K C
authors.initials: KC
authors.lastname: Noz
authors.forename: M
authors.initials: M
authors.lastname: Rademaker
authors.forename: P H
authors.initials: PH
authors.lastname: Van De Meide
authors.forename: J T
authors.initials: JT
authors.lastname: Van Dissel
authors.forename: B
authors.initials: B
authors.lastname: Thio
mesh_terms: D015331:Cohort Studies; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005650:Fumarates / Q000627:therapeutic use*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy*; D012720:Severity of Illness Index
chemical_list: D005650:Fumarates; D007378:Interleukins; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma