#5108 SUSTAINED IL-6 SECRETION CAN LEAD TO AN AMPLIFIED INFLAMMATORY RESPONSE, MEDIATED BY THE ACTIVATION OF STAT3 AND NFKB VIA THE IL-6 AMPLIFIER LOOP

Abstract Background and Aims Organ transplants are the preferred treatment for end-stage organ failure. Potent specific immunosuppressive agents have significantly decreased acute allograft rejection following renal transplantation. A significant barrier to long-term kidney outcomes is chronic antibody-mediated (CABMR). Chronic inflammation a major cause of late graft loss that mediated by soluble mediators released immune non-immune cells. IL-6 crucial cytokine plays central role in developing inflammation. Non-immune cells, such as fibroblasts, recently been identified mediating activating amplifier loop (IL-6+IL-17). Our Aim study: -to study effect IL-6+IL-17 on secretion culture supernatant fibroblasts derived from biopsy antibody (CABMR) patients; see anti-IL-6 (Tocilizumab)and anti-IL-17 tissue elucidate pro-inflammatory pathway leading increased induction Amplifier loop. Method Fibroblasts grafted CABMR patients (n = 6) were cultured stimulated with (20ng/ µl), IL-17(50ng/ plus IL-17 24 hours. Levels IL-6, MCP-1 CCL20 estimated supernatants ELISA marker activation. mRNA expression MCP1, CCL20, SOCS3 genes measured fibroblasts. Stimulated Renal fibroblast cells lysed Lysis buffer subjected SDS–PAGE western blotting anti-phospho-STAT3 anti-phospho-NFκB p65. Additionally, levels Healthy control 10), 20), non-CABMR 30) patients. Results synergistically induced more CCL-20 & production supernatant. Gene analysis was higher synergistic activation compared either or alone, while gene downregulated. results also suggested induces NFκB STAT3 signalling like concentrations sera (p<0.001). There reduction concentration inhibitor together reduced upregulated. Conclusion In humans after transplantation, an active responses. Inhibition Anti-IL-6 (Tocilizumab) inhibition Anti-IL-17 reduces markers injury (IL-6, CCL20) allografts. so, may be therapeutic target transplant rejection.