Methylation status of the IL-10 gene promoter in the peripheral blood mononuclear cells of rheumatoid arthritis patients

Interleukin 10(IL-10), as an immunoregulatory cytokine, plays an important role in rheumatoid arthritis (RA). IL-10 gene silencing is associated with the chromatin remodeling in differentiated Th1 and Th2 cells. To explore the rela- tionship between IL-10 promoter methylation and gene silencing in the pathogenesis of RA, IL-10 mRNA, protein expres- sion and promoter methylation status were analyzed in the peripheral blood mononuclear cells (PBMC) of 34 RA patients and 30 healthy controls by reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and methylation specific polymerase chain reaction (MSP), respectively. The results showed that IL-10 mRNA and protein expression in RA patients seemed to be lower than that in healthy controls, but there was no statistically significant difference (P0.05). IL-10 promoter was methylated at a frequency of 85.29% in RA cases, which was significantly higher than the percentage in healthy controls (43.33%) (χ 2 =12.439, P=0.000). IL-10 promoter methylation and mRNA expres- sion showed a strong negative correlation (r=?0.579, P=0.001). IL-10 promoter methylation, but not mRNA expression,also correlated statistically with the number of arthritic joints. However, there were no statistical correlations between IL-10 promoter methylation (or mRNA expression) and clinical indices of RA, such as the levels of erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and rheumatic factor (RF) or age (P0.05). These findings suggest that promoter methyla- tion may be a crucial mechanism of IL-10 gene inactivation in RA and IL-10 promoter CpG island hypermethylation might be involved in the occurrence and development of RA.