title: Interleukin (IL)-1 gene polymorphisms: relevance of disease severity associated alleles with IL-1beta and IL-1ra production in multiple sclerosis.
abstract: BACKGROUND
  Multiple sclerosis (MS) is an autoimmune disorder, with a considerable genetic influence on susceptibility and disease course. Cytokines play an important role in MS pathophysiology, and genes encoding various cytokines are logical candidates to assess possible associations with MS susceptibility and disease course. We previously reported an association of a combination of polymorphisms in the interleukin (IL)-1B and IL-1 receptor antagonist (IL-1RN) genes (i.e. IL-1RN allele 2+/IL-1B(+3959)allele 2-) with disease severity in MS. Extending this observation, we investigated whether IL-1beta and IL-1ra production differed depending on carriership of this gene combination.
  
  
  METHODS
  Twenty MS patients and 20 controls were selected based upon carriership of the specific combination. In whole blood, in vitro IL-1beta and IL-1ra production was determined by enzyme-linked immunosorbent-assay after 6 and 24 h of stimulation with lipopolysaccharide.
  
  
  RESULTS
  Carriers of the specific combination produced more IL-1ra, especially in MS patients, although not significantly. IL-1ra production was significantly higher in individuals homozygous for IL-1RN allele 2. In patients, Il-1ra production was higher and IL-1beta production lower compared with controls. In primary progressive patients, the IL-1beta /IL-1ra ratio was significantly lower than in relapsing-remitting patients.
  
  
  CONCLUSIONS
  Our results suggest higher in vitro IL-1ra production in carriers of IL-1RN allele 2, with an indication of an allelic dose-effect relationship.
authors.affiliation: Department of Neurology, Vrije Universiteit Medical Centre, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands. HM.Schrijver@vumc.nl
authors.forename: Hans M
authors.initials: HM
authors.lastname: Schrijver
authors.forename: Jaco
authors.initials: J
authors.lastname: van As
authors.forename: J Bart A
authors.initials: JB
authors.lastname: Crusius
authors.forename: Christien D
authors.initials: CD
authors.lastname: Dijkstra
authors.forename: Bernard M J
authors.initials: BM
authors.lastname: Uitdehaag
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D018628:Gene Dosage; D006579:Heterozygote; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000235:genetics* / Q000378:metabolism; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins