Are differences in interleukin 10 production associated with joint damage?
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.
Huizinga
T W
TW
Department of Rheumatology and. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Keijsers
V
V
Yanni
G
G
Hall
M
M
Ramage
W
W
Lanchbury
J
J
Pitzalis
C
C
Drossaers-Bakker
W K
WK
Westendorp
R G
RG
Breedveld
F C
FC
Panayi
G
G
Verweij
C L
CL
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*
D012333:RNA, Messenger; D016753:Interleukin-10