Anti-inflammatory Approach With Early Double Cytokine Blockade (IL-1? and TNF-?) Is Safe and Facilitates Engraftment in Islet Allotransplantation.

ABSTRACT: Background:The approach to reducing nonspecific inflammation after islet allotransplantation has been designed to improve engraftment, typically using 1 agent. We report results with the use of combination inflammatory blockade consisting of anti-interleukin (IL)-1? and tumor necrosis factor (TNF)-?. Methods:Nine patients underwent islet allotransplantation under a prospective research protocol using double cytokine blockade with anti-TNF-? (etanercept, d 0, 3, 7, 10) and IL-1? (anakinra, d 0-7) at the time of each islet infusion. The primary endpoint, assessed 2 years after the last islet transplant, was the elimination of severe hypoglycemic events and hypoglycemia unawareness, with proper glycemic control, and detectable serum C-peptide. Results:No thrombotic events or infectious complications were associated with combined IL-1? and TNF-? blockade. Six patients became insulin independent, 2 had partial function, and 1 had primary nonfunction. After 24-month follow-up, 6 of 9 patients had excellent glycemic control, hemoglobin A1c ?6.5%, and no episodes of hypoglycemia unawareness. Eight patients developed HLA alloantibodies at various time points (class 1, 5; class 2, 6), with enhanced T-cell alloreactivity. One patient retained good graft function despite having anti-glutamic acid decarboxylase 65 antibodies. Conclusions:The use of double cytokine blockade is safe, with reduction of inflammation at transplantation and presumably with better engraftment. However, it does not influence later islet loss from T-cell-mediated autoimmunity and alloimmunity, which require other strategies to maintain long-term islet function.

SUBMITTER: Onaca N 

PROVIDER: S-EPMC7056279 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature