Ryan Surujdin

Introduction. Rheumatoid Arthritis is an autoimmune disease that causes inflammation and progressive destruction of the joints. The disease affects about 1% of the population at any age, but occurs more often in women. It can be caused by numerous factors such as mutations in MHC class II loci, smoking, silica dust, vitamin D deficiency, or dysregulation of Interleukin (IL)-12 family cytokines¹. Studies show pro-inflammatory cytokines IL-12 and IL-23 and inflammatory processes are significantly upregulated in patients with Rheumatoid Arthritis (RA)². However, recent studies show that IL-35, a new member of the IL-12 cytokine family, are diminished in RA patients³. Therefore, IL-35 can be seen as a possible therapeutic target in preventing the progression in RA. Methods. Serum from control and RA patients were collected to measure IL-35 and Regulatory T Cell (Treg) levels using specific ELISAs and flow cytometry. In the murine model, synovial tissue samples in RA mice were stained to assess the progression of the disease and RT-PCR was performed to investigate the expression levels of pro-inflammatory and angiogenic factors. The impact of angiogenic factors were measured in cell cultures with treatment of IL-35. Results. Patients with RA showed a decrease in IL-35 and Tregs compared to normal patients. IL-35 and Treg treatments significantly reduced the expression of pro-inflammatory cytokines IL-17 and IFN-γ⁴. Synovial tissue of RA mice showed increased vascular formation, indicating the supportive role of angiogenesis in RA. Vascular Endothelial Growth Factors (VEGF) and pro-inflammatory cytokines were downregulated in with IL-35 treatments⁵. The inhibition of VEGF by IL-35 was later proven in cell culture by showing a decease in cell growth and movement using cell migration and scratch test assays⁶. Conclusion. Studies have shown that IL-35 is significantly diminished in RA patients, indicating its protective role against RA. Blood vessel growth and pro-inflammatory cytokines were upregulated to increase the progression of RA. However, IL-35 treatments proved to diminish cell migration and growth in VEGF supported cells. Because of the recent investigation of IL-12’s newest cytokine member, IL-35, it poses as a possible treatment route for preventing RA.

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