longitudinal study to investigate the role of IL-6 and IL-7 in the pathologenesis of early rheumatoid arthritis

ABSTRACT

Previous researches indicate that IL-6 is a pro-inflammatory cytokine in RA that can drive Th17 cell development in mice and humans. Data from experimental arthritis models suggest that Th17 cells are pathogenic via production of the pro-inflammatory cytokines IL-17 and TNF alpha, leading to monocyte and fiboblast activation, and involvement in osteoclastogeneis and joint damage. The aim of this study is to investigate if interleukin-6 [IL-6] and/or interleukin-17 [IL-17] and Th17 cells are biomarkers for disease progression and severity in early Undifferentiated Arthritis [UA] and/Rheumatoid Arthritis [RA] patients. We performed a longitudinal study recruiting 20 patients with either undifferentiated inflammatory arthritis or early rheumatoid arthritis. We also recruited 30 age [mean = 46] and sex-matched healthy controls. The patients were assessed at baseline, 6 and 12 months for the American College of Rheumatology [ACR] criteria, Rheumatoid factor [RF], Anti Citrullinated Peptides [Anti-CCP], ESR, CRP, X-Ray of the hands and feet, joint count, patient global assessment, DAS28 and Quality of Life [HAQ] measurements. Peripheral blood and serum samples were taken and PBMC isolated. Cell subset analysis [CD3, CD4/CD8, and CD14] was performed ex vivo. Peripheral blood monocytes in RA and UDA showed the proportion of IL6 CD14+Monocytes significantly higher in RA patients at base line than the UDA. Sero-positive patients were higher in the proportion of [Total IL17 CD3 +CD4+Tcells, IFNgamma+IL17+CD3+CD4+Tcells, IL6 CD14+Monocytes] than the sero-negative patients but that differences did not reach statistical significance. The longitudinal follow up for the early arthritis group, showed a significant change in the%IL6 Monocytes. The proportion of IL6 and IL17 in peripheral blood of early rheumatoid arthritis shows a weak correlation with disease activity which could not be an ideal biomarker for disease activity in comparison to synovial level of these cytokines