title: Association of the risk of osteoarthritis with high innate production of interleukin-1beta and low innate production of interleukin-10 ex vivo, upon lipopolysaccharide stimulation.
abstract: OBJECTIVE
  In a sibpair study of osteoarthritis (OA) patients, we investigated whether, upon stimulation with lipopolysaccharide (LPS), variations in the innate ex vivo production of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), IL-10, and tumor necrosis factor alpha (TNFalpha) in whole-blood assays contribute to the risk of OA.
  
  
  METHODS
  Data from 305 patients with OA at multiple sites (hand, knee, hip, and spine), whose median age was 60 years (range 43-79 years), were compared with those from 137 controls. OA was defined in accordance with the American College of Rheumatology criteria. Whole-blood samples were stimulated with LPS (10 ng/ml). In the supernatants, cytokines were measured by enzyme-linked immunosorbent assay. Odds ratios (ORs) were used as measures of the relative risk of OA in relation to quartiles of IL-1beta, IL-1Ra, TNFalpha, and IL-10 production. The ORs were adjusted for sex and age, and 95% confidence intervals (95% CIs) were computed using robust standard errors to take into account the intrafamily effect.
  
  
  RESULTS
  Subjects in the highest quartile of IL-1beta and IL-1Ra had an increased risk of OA (OR 3.3, 95% CI 1.4-7.9 and OR 8.0, 95% CI 3.7-17.4, respectively), while subjects in the lowest quartile of IL-10 had a 3-fold increased risk of OA (OR 3.1, 95% CI 1.5-6.5). High innate ex vivo production of TNFalpha was not associated with an increased risk of OA.
  
  
  CONCLUSIONS
  Subjects with a high innate ex vivo production of IL-1beta and IL-1Ra and low innate ex vivo production of IL-10 have an increased risk of OA. These results suggest that a proportion of the genetic susceptibility to OA may be encoded for by variations in innate cytokine activity.
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Naghmeh
authors.initials: N
authors.lastname: Riyazi
authors.forename: Eline
authors.initials: E
authors.lastname: Slagboom
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: Ingrid
authors.initials: I
authors.lastname: Meulenbelt
authors.forename: Jeanine J
authors.initials: JJ
authors.lastname: Houwing-Duistermaat
authors.forename: Herman M
authors.initials: HM
authors.lastname: Kroon
authors.forename: Dirkjan
authors.initials: D
authors.lastname: van Schaardenburg
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: Ferdinand C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: Margreet
authors.initials: M
authors.lastname: Kloppenburg
mesh_terms: D000328:Adult; D000368:Aged; D004926:Escherichia coli; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood / Q000276:immunology*; D012306:Risk
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D016753:Interleukin-10