title: Innate production of tumour necrosis factor alpha and interleukin 10 is associated with radiological progression of knee osteoarthritis.
abstract: OBJECTIVE
  Inflammation may contribute to progression of knee osteoarthritis (OA). Therefore, we investigated whether innate differences in the inflammatory response regarding cytokine production were associated with radiological progression of knee OA.
  
  
  METHODS
  Symptomatic patients with knee OA (n = 89) were included. Standardised posteroanterior knee radiographs were obtained at baseline and after 24 months. Medial and lateral tibiofemoral joint space narrowing (JSN) was graded with the Altman atlas. Radiological progression was defined as an increase of at least one score in JSN total scores. Whole blood samples were stimulated with lipopolysaccharide (LPS) (10 ng/ml). Relative risks (RR) with 95% CIs of OA progression in relation to quartiles of innate ex vivo production of interleukin (IL)1beta, tumour necrosis factor (TNF)alpha, IL1 receptor antagonist (Ra) and IL10 were calculated.
  
  
  RESULTS
  Progression of JSN was present in 29 (33.7%) of 86 followed patients after 2 years. Patients in the highest quartile of TNFalpha production had a sixfold increased risk of JSN progression (age, sex and body mass index adjusted RR 6.1, 95% CI 1.4 to 9.8) and patients in the highest quartile of IL10 production had a fourfold increased risk of JSN progression (age, sex and body mass index adjusted RR 4.3, 95% CI 1.7 to 6.2), both in comparison with those patients in the lowest quartile. No significant associations were found between variations in IL1beta and IL1Ra production and JSN progression.
  
  
  CONCLUSIONS
  The innate capacity to produce TNFalpha and IL10 upon LPS stimulation is associated with radiological progression of knee OA, even over a relatively short follow-up period of 2 years.
authors.affiliation: Leiden University Medical Centre, Department of Rheumatology, C01-R, PO Box 9600, 2300 RC Leiden, The Netherlands. S.A.Scheepers@lumc.nl
authors.forename: S
authors.initials: S
authors.lastname: Botha-Scheepers
authors.forename: I
authors.initials: I
authors.lastname: Watt
authors.forename: E
authors.initials: E
authors.lastname: Slagboom
authors.forename: A J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: I
authors.initials: I
authors.lastname: Meulenbelt
authors.forename: F R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: F C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: T W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: M
authors.initials: M
authors.lastname: Kloppenburg
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016001:Confidence Intervals; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016753:Interleukin-10 / Q000097:blood* / Q000276:immunology; D053583:Interleukin-1beta / Q000097:blood / Q000276:immunology; D007719:Knee Joint / Q000000981:diagnostic imaging*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging* / Q000276:immunology*; D011859:Radiography; D012306:Risk; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000276:immunology
chemical_list: D015415:Biomarkers; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10