Rheumatology 2000; 39: 1180-1188
© 2000 British Society for Rheumatology
Are differences in interleukin 10 production associated with joint damage?
Department of Rheumatology and
2 Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands and
1 Department of Rheumatology, GKT School of Medicine, Guy's Hospital Campus, King's College, London SE1 9RT, UK
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.
Discussion. 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.
KEY WORDS: Interleukin 10, Joint damage, Genotypes.
Correspondence to: T. W. J. Huizinga, Leiden University Medical Center, Department of Rheumatology, C4-R, P. O.. Box, 9600, 2300 RC Leiden, The Netherlands.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R Dieguez-Gonzalez, S Akar, M Calaza, E Perez-Pampin, J Costas, M Torres, J L Vicario, M L Velloso, F Navarro, J Narvaez, et al. Genetic variation in the nuclear factor {kappa}B pathway in relation to susceptibility to rheumatoid arthritis Ann Rheum Dis, April 1, 2009; 68(4): 579 - 583. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Crilly, J. Hamilton, C. J. Clark, A. Jardine, and R. Madhok Analysis of the 5' flanking region of the interleukin 10 gene in patients with systemic sclerosis Rheumatology, November 1, 2003; 42(11): 1295 - 1298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Pipitone, G. H. Kingsley, A. Manzo, D. L. Scott, and C. Pitzalis Current concepts and new developments in the treatment of psoriatic arthritis Rheumatology, October 1, 2003; 42(10): 1138 - 1148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Asadullah, W. Sterry, and H. D. Volk Interleukin-10 Therapy--Review of a New Approach Pharmacol. Rev., June 1, 2003; 55(2): 241 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D Lio, L Scola, A Crivello, G Colonna-Romano, G Candore, M Bonafe, L Cavallone, F Marchegiani, F Olivieri, C Franceschi, et al. Inflammation, genetics, and longevity: further studies on the protective effects in men of IL-10 -1082 promoter SNP and its interaction with TNF-{alpha} -308 promoter SNP J. Med. Genet., April 1, 2003; 40(4): 296 - 299. [Full Text] [PDF]
|
|
|
|
|
|
K. MacKay, A. Milicic, D. Lee, M. Tikly, S. Laval, J. Shatford, and P. Wordsworth Rheumatoid arthritis susceptibility and interleukin 10: a study of two ethnically diverse populations Rheumatology, January 1, 2003; 42(1): 149 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gerli, C. Lunardi, and C. Pitzalis Unmasking the anti-inflammatory cytokine response in rheumatoid synovitis Rheumatology, December 1, 2002; 41(12): 1341 - 1345. [Full Text] [PDF]
|
|
|
|
 |
|
 A. W. Gibson, J. C. Edberg, J. Wu, R. G. J. Westendorp, T. W. J. Huizinga, and R. P. Kimberly Novel Single Nucleotide Polymorphisms in the Distal IL-10 Promoter Affect IL-10 Production and Enhance the Risk of Systemic Lupus Erythematosus J. Immunol., March 15, 2001; 166(6): 3915 - 3922. [Abstract] [Full Text] [PDF]
|
|