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
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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.
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