title: Are differences in interleukin 10 production associated with joint damage?
abstract: OBJECTIVE
  Constitutive differences between individuals in cytokine production may determine the variation in the course of inflammatory arthritis.
  
  
  METHODS
  The association between interleukin 10 (IL-10) production and joint destruction was studied by comparing IL-10 mRNA content in synovial biopsies from seven patients with destructive joint disease and six patients with non-destructive joint disease. The IL-10 mRNA content was 0.4 +/- 0.6 arbitrary units in erosive joints compared with 2.3 +/- 1.2 arbitrary units in non-erosive joints (P: < 0.03, Mann-Whitney U:-test). As this difference suggested that IL-10 production was associated with joint destruction, we tested whether the IL-10 locus determined the extent of joint damage.
  
  
  RESULTS
  Innate differences in IL-10 production are locus-dependent. In line with these data, we showed that innate differences in IL-10 protein production were also present as differences in IL-10 mRNA levels. We tested if polymorphisms in the promoter of IL-10 were associated with the extent of joint damage.
  
  
  CONCLUSIONS
  In a cohort study of female rheumatoid arthritis patients followed for 12 yr, the extent of joint destruction differed significantly between patients with different IL-10 genotypes. In patients with the -1082AA genotype who were studied prospectively, the mean increase in radiographic damage score (modified Sharp score of X-rays of hands and feet) during the first 6 yr was 9 +/- 9 per yr vs 19 +/- 16 per yr for patients with the genotype -1082GG (P: < 0.02). In line with these data, cultures of endotoxin-stimulated whole blood from 158 donors showed that the presence of the allele associated with less joint destruction correlated with slightly higher IL-10 production.
  
  
  CONCLUSIONS
  Both the immunogenetic and the synovial biopsies suggest that a variation in IL-10 production is associated with joint destruction.
authors.affiliation: Department of Rheumatology and. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: T W
authors.initials: TW
authors.lastname: Huizinga
authors.forename: V
authors.initials: V
authors.lastname: Keijsers
authors.forename: G
authors.initials: G
authors.lastname: Yanni
authors.forename: M
authors.initials: M
authors.lastname: Hall
authors.forename: W
authors.initials: W
authors.lastname: Ramage
authors.forename: J
authors.initials: J
authors.lastname: Lanchbury
authors.forename: C
authors.initials: C
authors.lastname: Pitzalis
authors.forename: W K
authors.initials: WK
authors.lastname: Drossaers-Bakker
authors.forename: R G
authors.initials: RG
authors.lastname: Westendorp
authors.forename: F C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: G
authors.initials: G
authors.lastname: Panayi
authors.forename: C L
authors.initials: CL
authors.lastname: Verweij
mesh_terms: D000328:Adult; D000368:Aged; D001168:Arthritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D001706:Biopsy; D002908:Chronic Disease; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D015870:Gene Expression / Q000276:immunology; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D011859:Radiography; D013583:Synovial Membrane / Q000000981:diagnostic imaging / Q000473:pathology*
chemical_list: D012333:RNA, Messenger; D016753:Interleukin-10