TNF-Α, IL-1β and IL-6 Cytokine Gene Expression in Synovial Fluid of Rheumatoid Arthritis and Osteoarthritis Patients and Their Relationship with Gene Polymorphisms

Abstract

Objective: To analyse and compare TNF-α, IL-1β and IL-6 mRNA expression of rheumatoid arthritis (RA) and osteoarthritis patients (OA) and to study the relationship between mRNA expression and promoter polymorphisms of these genes in RA patients. Method: A total of 20 RA, 10 OA and 10 healthy controls were taken in this study. The mRNA expression was quantified by qRT-PCR method and polymorphic analysis done by PCR-RFLP method. Result: TNF-α, IL-1β and IL-6 mRNA expression was significantly increased in the synovial fluid of both RA and OA patients as compared to healthy controls but with a higher fold change in RA than OA with TNF-α: 10.70 fold in RA vs 3.58 fold in OA; IL-1β: 5.61 fold in RA vs 2.42 fold in OA and IL-6: 2.58 fold in RA vs 1.70 fold in OA. The TNF-α and IL-1β mRNA expression was higher in RA patients with higher DAS28 Score (p = 0.02 and p = 0.009 respectively). TNF-α and IL-1β mRNA expression was significantly higher in the carriers of TNF-α-238 GG (p = 0.04) and IL-1β-511 TT (p = 0.03) genotypes respectively. Conclusion: We conclude that TNF-α, IL-1β and IL-6 cytokines play an important role in the pathogenesis and disease severity of RA. Also, the difference in cytokine gene expression between RA and OA is more quantitative than qualitative. Therefore, suggesting a more intense inflammatory nature of RA than OA. Moreover, the TNF-α-238 GG and IL-1β-511 TT genotypes are associated with higher mRNA expression, therefore are susceptibility markers to RA.