Are differences in interleukin 10 production associated with joint damage?

Objective. Constitutive differences between individuals in cytokine product ion may determine the variation in the course of inflammatory arthritis. Methods. The association between interleukin 10 (IL-10) production and join t destruction was studied by comparing IL-10 mRNA content in synovial biops ies from seven patients with destructive joint disease and six patients wit h non-destructive joint disease. The IL-10 mRNA content was 0.4 +/- 0.6 arb itrary 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 sug gested that IL-10 production was associated with joint destruction, we test ed whether the IL-10 locus determined the extent of joint damage. Results. Innate differences in IL-10 production are locus-dependent. In lin e with these data, we showed that innate differences in IL-10 protein produ ction were also present as differences in IL-10 mRNA levels. We tested if p olymorphisms in the promoter of IL-10 were associated with the extent of jo int damage. Discussion. In a cohort study of female rheumatoid arthritis patients follo wed for 12 yr, the extent of joint destruction differed significantly betwe en patients with different IL-10 genotypes. In patients with the -1082AA ge notype who were studied prospectively, the mean increase in radiographic da mage score (modified Sharp score of X-rays of hands and feet) during the fi rst 6 yr was 9 +/- 9 per yr vs 19 +/- 16 per yr for patients with the genot ype -1082GG (P < 0.02). In line with these data, cultures of endotoxin-stim ulated whole blood from 158 donors showed that the presence of the allele a ssociated 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.