Article Text

Download PDFPDF
Ex vivo interleukin 1 receptor antagonist production on lipopolysaccharide stimulation is associated with rheumatoid arthritis and with joint damage
  1. J K de Vries-Bouwstra1,
  2. Y P M Goekoop-Ruiterman2,
  3. J Wesoly2,
  4. H J Hulsmans3,
  5. A J M de Craen4,
  6. F C Breedveld2,
  7. B A C Dijkmans1,
  8. C F Allaart2,
  9. T W J Huizinga2
  1. 1Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands
  2. 2Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3Department of Rheumatology, Hagaziekenhuis, The Hague, The Netherlands
  4. 4Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to:
    J K de Vries-Bouwstra
    Department of Rheumatology C1R, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands; jkdevriesbouwstra{at}


Objectives: (1) To assess innate ex vivo production of interleukin 1β (IL1β) and interleukin 1 receptor antagonist (IL1Ra) in patients with recent-onset rheumatoid arthritis (RA) as compared with healthy controls; (2) to assess the association of ex vivo IL1β and IL1Ra production with progression of joint damage in RA; (3) to determine whether differences in ex vivo IL1β production are explained by distribution of the IL1β single nucleotide polymorphism C-511T.

Methods: Levels of IL1β and IL1Ra (measured by ELISA after whole-blood stimulation with lipopolysaccharide) and distribution of IL1β C-511T were compared in 76 patients with recent-onset RA who had received no disease-modifying antirheumatic drugs (DMARDs), and 63 healthy controls. ORs for RA based on ex vivo IL1β and IL1Ra production were calculated. Association of ex vivo IL1β and IL1Ra production with progression of joint damage (Sharp–van der Heijde score over 2 years) was determined by linear regression with correction for baseline characteristics.

Results: Patients with recent-onset RA showed lower ex vivo IL1β and higher ex vivo IL1Ra production than healthy controls (p<0.001), with ORs for RA of 2.4 (95% CI 1.2 to 4.9) for low IL1β-producers and 7.6 (95% CI 3.2 to 18.0) for high IL1Ra-producers. High ex vivo IL1Ra production was associated with progression of joint damage (p = 0.01). The IL1β C-511T genotype distribution was not significantly different between patients and controls.

Conclusions: Patients with recent-onset RA had decreased ex vivo IL1β production and increased ex vivo IL1Ra production compared with controls. Ex vivo IL1Ra production is an independent predictor of progression of joint damage in recent-onset RA.

  • DMARD, disease-modifying antirheumatic drug
  • HAQ, health assessment questionnaire
  • IL1 interleukin 1
  • IL1β, interleukin 1 beta
  • IL1Ra, interleukin 1 receptor antagonist
  • LPS, lipopolysaccharide
  • RA, rheumatoid arthritis
  • SHS, Sharp–van der Heijde score

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Published Online First 11 January 2007

  • Funding: The BeSt Study was supported by a grant from the Dutch College for Health Insurance Companies (CVZ). Additional funding was from Centocor and Schering-Plough.

  • Competing interests: None.

  • The Dutch College for Health Insurance Companies, Centocor and Schering-Plough had no role in the design of the study, the collection, the analysis and interpretation of the data, the writing of the report or the decision to submit.