Dipeptidyl peptidase 4 inhibitors: Applications in innate immunity?

Biochem Pharmacol. 2021 Jun:188:114517. doi: 10.1016/j.bcp.2021.114517. Epub 2021 Mar 13.

Abstract

Dipeptidyl peptidase (DPP)-4 inhibitors are a class of orally available, small molecule inhibitors that prolong the insulinotropic activity of the incretin hormone glucagon-like peptide-1 (GLP-1) and are highly effective for the treatment of Type-2 diabetes. DPP4 can also cleave several immunoregulatory peptides including chemokines. Emerging evidence continues to implicate DPP4 inhibitors as immunomodulators, with recent findings suggesting DPP4 inhibitors modify specific aspects of innate immunity. This review summarises recent insights into how DPP4 inhibitors could be implicated in endothelial, neutrophil and monocyte/macrophage mediated immunity. Additionally, this review highlights additional avenues of research with DPP4 inhibitors in the context of the COVID-19 pandemic.

Keywords: DPP4 inhibitor; Dipeptidyl peptidase; Immunity; Innate immunity; Macrophage; Neutrophil; Sitagliptin.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • COVID-19 / immunology
  • COVID-19 Drug Treatment*
  • Dipeptidyl-Peptidase IV Inhibitors / chemistry
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Glucagon-Like Peptide 1 / immunology
  • Humans
  • Immunity, Innate / drug effects*
  • Immunity, Innate / immunology
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / immunology

Substances

  • Anti-Inflammatory Agents
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucagon-Like Peptide 1