Administration of IL-1 Trap prolongs survival of transplanted pancreatic islets to type 1 diabetic NOD mice

• We previously reported that IL-1 Trap (a hybrid molecule consisting of the extracellular domain of IL-1 receptor accessory protein and IL-1 receptor type 1 arranged inline and fused to the Fc-portion of IgG1) can protect rat pancreatic islets in vitro against noxious effects induced by IL-1 beta. In this study we tested the effect of administration of a murine IL-1 Trap on the recurrence of disease (ROD) model in non-obese diabetic (NOD) mice. Spontaneously diabetic female NOD mice received implantation of a curative number (600) of syngeneic pancreatic islets beneath their left kidney capsule from young healthy NOD mouse donors. Once a day, the mice were injected subcutaneously with IL-1 Trap (30 mg/kg bodyweight), or an equimolar dose Fc-control protein (8.4 mg/kg bodyweight) or saline. The treatments were maintained until ROD (i.e. a blood glucose value >= 11.1 mM for 2 consecutive days) or until 5 days after transplantation. 3 out of 11 mice treated with IL-1 Trap showed a significantly increased graft survival compared to all other mice, and analysis of relative cytokine mRNA levels in isolated spleen cells showed elevated IL-4 mRNA levels, but no differences in FoxP3 or iNOS staining of grafts, from mice treated with IL-1 Trap, at both endpoints, compared to both control groups. Administration of IL-1 Trap counteracts islet cell destruction in the NOD mouse model of type 1 diabetes. In part this could be due to a shift towards Th2 cytokine production seen in IL-1 Trap treated animals. 

Nyckelord

Type 1 diabetes

Non-obese diabetic mice

Interleukin-1 Trap

Recurrence of disease model

Interleukin-4

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)