Interleukin-1 receptor antagonist: a new therapy for type 2 diabetes mellitus

Abstract

Various complex mechanisms and their multifactorial pathways decisively provoke low-grade local and systemic inflammation in β-cells of pancreatic islets and peripheral tissues to induce β-cells' dysfunction and apoptosis, insulin resistance, and ultimately, overt type 2 diabetes mellitus (T2DM). Conventional antidiabetic agents are being less popular, as they have some potential adverse effects. Currently, many anti-inflammatory therapeutic modalities are being investigated to abate the infuriating effects of inducers of T2DM and among them, interleukin-1 receptor antagonist (IL-1Ra) is the only one that has been approved by US Food and Drug Administration. We have compared IL-1Ra with other anti-inflammatory agents and conventional antidiabetic agents. Although, IL-1Ra has broad-spectrum anti-inflammatory activities, it also has some limitations due to its short half-life. To overcome the problem of short half-life of IL-1Ra, recently, we fused IL-1Ra in recombinant human serum albumin and expressed it in Pichia pastoris. Its bioactivity was also checked by IL-1-induced A375.S2 apoptotic cells. Furthermore, we have also formulated IL-1Ra with Pluronic F-127-based thermosensitive gel and investigated its in vitro characteristics to prolong its therapeutic effects. Further studies are required to investigate its therapeutic effects against diabetes and diabetes-associated complications.