Therapeutic vaccine against IL-1β improved glucose control in a mouse model of type 2 diabetes.

AIMS: Inflammation is strongly associated with the mechanism of β-cell failure in type 2 diabetes mellitus (T2DM). Blockade of the key proinflammatory cytokine IL-1β has been implicated as a promising therapeutic strategy for the prevention and treatment of type 2 diabetes. In this study, we developed an IL-1β-targeted therapeutic vaccine consisting of an IL-1β epitope peptide (A1β) and assessed its efficacy on a diabetic KK-Ay mouse model.

MAIN METHODS: KK-Ay mice were immunized with A1β for three injections at a 2-week interval. The induced antibody titers, body weights and blood glucose levels were monitored every two weeks. Then the intraperitoneal glucose tolerance test and insulin tolerance test were performed. The β-cell mass, β-cell apoptosis and proliferation were evaluated by immunofluorescence. IL-1β gene expression in islets was also measured by quantitative RT-PCR.

KEY FINDINGS: A1β immunization induced robust antibody responses, reduced body weight gain, improved glucose tolerance and insulin sensitivity in KK-Ay mice. Moreover, A1β restored β-cell mass, inhibited β-cell apoptosis, enhanced β-cell proliferation and downregulated IL-1β expression.

SIGNIFICANCE: The novel IL-1β-targeted epitope vaccine has the therapeutic potential for T2DM.