Anti-Inflammatory Strategies in Intrahepatic Islet Transplantation: A Comparative Study in Preclinical Models. Issue 2 (February 2018)

• Record Type: Journal Article
• Authors: Citro, Antonio; Cantarelli, Elisa; Pellegrini, Silvia; Dugnani, Erica; Piemonti, Lorenzo
• Is Part Of: Transplantation. Volume 102:Issue 2(2018)
• Publication Date: 2018-02
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000001925
• Languages: English
• ISSNs: 0041-1337

Abstract

Abstract : Background: The identification of pathway(s) playing a pivotal role in peritransplant detrimental inflammatory events represents the crucial step toward a better management and outcome of pancreatic islet transplanted patients. Recently, we selected the CXCR1/2 inhibition as a relevant strategy in enhancing pancreatic islet survival after transplantation. Methods: Here, the most clinically used anti-inflammatory compounds (IL1-receptor antagonist, steroids, and TNF-α inhibitor) alone or in combination with a CXCR1/2 inhibitor were evaluated in their ability to improve engraftment or delay graft rejection. To rule out bias related to transplantation site, we used well-established preclinical syngeneic (250 C57BL/6 equivalent islets in C57BL/6) and allogeneic (400 Balb/c equivalent islets in C57BL6) intrahepatic islet transplantation platforms. Results: In mice, we confirmed that targeting the CXCR1/2 pathway is crucial in preserving islet function and improving engraftment. In the allogeneic setting, CXCR1/2 inhibitor alone could reduce the overall recruitment of transplant-induced leukocytes and significantly prolong the time to graft rejection both as a single agent and in combination with immunosuppression. No other anti-inflammatory compounds tested (IL1-receptor antagonist, steroids, and TNF-α inhibitor) alone or in combination with CXCR1/2 inhibitor improve islet engraftment and significantly delay graft rejection in the presence of MMF + FK-506 immunosuppressive treatment. Conclusions: These findings indicate that only the CXCR1/2-mediated axis plays a crucial role in controlling the islet damage and should be a target for intervention to improve the efficiency of islet transplantation. Abstract : This report covers novel anti-inflammatory strategies for intrahepatic islet transplantation. The authors demonstrate that a CXCR1/2 inhibitor when given with MMF+tacrolimus, improves islet engraftment and delays graft rejection. Supplemental digital content is available in the text.