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

Abstract

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.

• Authors: Yue Zhang, Xiao-Lin Yu, Jun Zha, Li-Zhen Mao, Jia-Qian Chai, Rui-Tian Liu
• Journal: Life sciences (Life Sci) Vol. 192 Pg. 68-74 (Jan 01 2018) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 29155303 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies
• Blood Glucose
• Epitopes
• Immunoglobulin G
• Interleukin-1beta
• Vaccines

Topics

• Animals
• Antibodies (analysis)
• Apoptosis
• Blood Glucose (metabolism)
• Body Weight
• Cell Proliferation
• Diabetes Mellitus, Type 2 (genetics, metabolism, therapy)
• Disease Models, Animal
• Down-Regulation (genetics, immunology)
• Epitopes (immunology)
• Glucose Tolerance Test
• Immunoglobulin G (analysis, biosynthesis)
• Insulin Resistance
• Insulin-Secreting Cells (metabolism)
• Interleukin-1beta (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Vaccines (immunology, therapeutic use)