Weekly injection of IL-2 using an injectable hydrogel reduces autoimmune diabetes incidence in NOD mice

Diabetologia. 2021 Jan;64(1):152-158. doi: 10.1007/s00125-020-05314-1. Epub 2020 Oct 30.

Abstract

Aims/hypothesis: IL-2 injections are a promising therapy for autoimmune type 1 diabetes but the short half-life of this cytokine in vivo limits effective tissue exposure and necessitates frequent injections. Here we have investigated whether an injectable hydrogel could be used to promote prolonged IL-2 release in vivo.

Methods: Capitalising on the IL-2-binding capabilities of heparin, an injectable hydrogel incorporating clinical-grade heparin, collagen and hyaluronan polymers was used to deliver IL-2. The IL-2-release kinetics and in vivo stability of this material were examined. The ability of soluble IL-2 vs hydrogel-mediated IL-2 injections to prevent autoimmune diabetes in the NOD mouse model of type 1 diabetes were compared.

Results: We observed in vitro that the hydrogel released IL-2 over a 12-day time frame and that injected hydrogel likewise persisted 12 days in vivo. Notably, heparin binding potentiates the activity of IL-2 and enhances IL-2- and TGFβ-mediated expansion of forkhead box P3-positive regulatory T cells (FOXP3+ Tregs). Finally, weekly administration of IL-2-containing hydrogel partially prevented autoimmune diabetes while injections of soluble IL-2 did not.

Conclusions/interpretation: Hydrogel delivery may reduce the number of injections required in IL-2 treatment protocols for autoimmune diabetes. Graphical abstract.

Keywords: Autoimmune; Controlled release; Diabetes; Heparin; Hyaluronan; Hydrogels; IL-2; Treg.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't