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

backgroundThe 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)-1β and tumor necrosis factor (TNF)-α.

methodsNine patients underwent islet allotransplantation under a prospective research protocol using double cytokine blockade with anti-TNF-α (etanercept, d 0, 3, 7, 10) and IL-1β (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.

resultsNo thrombotic events or infectious complications were associated with combined IL-1β and TNF-α 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.

conclusionsThe 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.