Objective: Fibroblasts from grafted kidney from CABMR patients (n=6) were cultured and stimulated with IL-6 (20ng/ µl), IL-17(50ng/ µl), IL-6 plus IL-17 for 24 hours. Levels of IL-6, MCP-1 and CCL20 were estimated in culture supernatants by ELISA as marker of IL-6 amplifier loop activation. mRNA expression of IL-6, MCP1, CCL20, and SOCS3 genes were measured in the stimulated fibroblasts. Additionally, IL-6, MCP1, and CCL20 levels were measured in Healthy control (n=10), CABMR (n=20), and non-CABMR (n=30) patients. Methods: IL-6 and IL-17 synergistically induced more IL-6, CCL-20 & MCP-1 production from fibroblasts. Fig1 Gene expression analysis of IL-6, MCP1, and CCL20 was significantly higher with synergistic activation of IL-6 and IL-17 as compared to either IL-6 or IL-17 alone, while SOCS3 gene expression was downregulated. Fig 3. Additionally, concentrations of IL-6, CCL-20 & MCP-1 in sera were significantly higher in CABMR patients compared to non-rejection patients (p<0.001). Fig 2 There was a significant reduction in IL-6 concentration in culture supernatant with IL-6 and IL-17 inhibitor together Fig 4 and mRNA expression of IL-6 and MCP-1 was significantly reduced. Fig 5 Results: CABMR is perpetuated by inflammation amplifier loop or synergistic induction of IL-6 and IL-17. Inhibition of IL-6 with Anti-IL-6 (Tocilizumab) and IL-17 with Anti-IL-17 together reduces the tissue injury marker (IL-6, MCP1, CCL20) and allograft rejection.                                                                       Conclusions: Objective: Recently, non-immune cells like fibroblast have been postulated to mediate allograft rejection via activation of IL-6 amplifier loop (IL-6+IL-17). We evaluated IL-6 amplifier loop activation by IL-6 and Il-17 in chronic antibody mediated rejection (CABMR). Methods: Fibroblasts from grafted kidney from CABMR patients (n=6) were cultured and stimulated with IL-6 (20ng/ µl), IL-17(50ng/ µl), IL-6 plus IL-17 for 24 hours. Levels of IL-6, MCP-1 and CCL20 were estimated in culture supernatants by ELISA as marker of IL-6 amplifier loop activation. mRNA expression of IL-6, MCP1, CCL20, and SOCS3 genes were measured in the stimulated fibroblasts. Additionally, IL-6, MCP1, and CCL20 levels were measured in Healthy control (n=10), CABMR (n=20), and non-CABMR (n=30) patients. Results: IL-6 and IL-17 synergistically induced more IL-6, CCL-20 & MCP-1 production from fibroblasts. Fig1 Gene expression analysis of IL-6, MCP1, and CCL20 was significantly higher with synergistic activation of IL-6 and IL-17 as compared to either IL-6 or IL-17 alone, while SOCS3 gene expression was downregulated. Fig 3. Additionally, concentrations of IL-6, CCL-20 & MCP-1 in sera were significantly higher in CABMR patients compared to non-rejection patients (p<0.001). Fig 2 There was a significant reduction in IL-6 concentration in culture supernatant with IL-6 and IL-17 inhibitor together Fig 4 and mRNA expression of IL-6 and MCP-1 was significantly reduced. Fig 5 Conclusions: CABMR is perpetuated by inflammation amplifier loop or synergistic induction of IL-6 and IL-17. Inhibition of IL-6 with Anti-IL-6 (Tocilizumab) and IL-17 with Anti-IL-17 together reduces the tissue injury marker (IL-6, MCP1, CCL20) and allograft rejection.