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 beta-cell failure in type 2 diabetes mellitus (T2DM). Blockade of the key proinflammatory cytokine IL-1 beta has been implicated as a promising therapeutic strategy for the prevention and treatment of type 2 diabetes. In this study, we developed an IL-1 beta-targeted therapeutic vaccine consisting of an IL-1 beta epitope peptide (A1 beta) and assessed its efficacy on a diabetic KK-A(y) mouse model. Main methods: KK-A(y) mice were immunized with A1 beta 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 beta-cell mass, beta-cell apoptosis and proliferation were evaluated by immunofluorescence. IL-1 beta gene expression in islets was also measured by quantitative RT-PCR. Key findings: A1 beta immunization induced robust antibody responses, reduced body weight gain, improved glucose tolerance and insulin sensitivity in KK-A(y) mice. Moreover, A1 beta restored beta-cell mass, inhibited beta-cell apoptosis, enhanced beta-cell proliferation and downregulated IL-1 beta expression. Significance: The novel IL-1 beta-targeted epitope vaccine has the therapeutic potential for T2DM.