The effect of interleukin-22 treatment on autoimmune diabetes in the NOD mouse

• Published in: Diabetologia 2017-11, Vol.60 (11), p.2256-2261
• Main Authors: Borg, Danielle J., Wang, Ran, Murray, Lydia, Tong, Hui, Steptoe, Raymond J., McGuckin, Michael A., Hasnain, Sumaira Z.
• Format: Article
• Language: English
• Subjects: Animals; Autoimmune diseases; Beta cells; Biological Assay; Blood glucose; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - immunology; Endoplasmic reticulum; Fasting; Female; Human Physiology; In Vitro Techniques; Insulin; Insulitis; Interleukin 22; Interleukins - therapeutic use; Internal Medicine; Laboratory testing; Lipopolysaccharides; Macrophages; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; Mice, Inbred NOD; Mucosa; Rodents
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-017-4392-2

Aims/hypothesis The aim of this study was to determine whether therapy with the cytokine IL-22 could be used to prevent the development of, or treat, autoimmune diabetes in the NOD mouse. Methods Six-week-old NOD mice were administered bi-weekly either recombinant mouse IL-22 (200 ng/g) or PBS (vehicle control) intraperitoneally until overt diabetes was diagnosed as two consecutive measurements of non-fasting blood glucose ≥ 11 mmol/l. At this time, NOD mice in the control arm were treated with LinBit insulin pellets and randomised to bi-weekly therapeutic injections of either PBS or IL-22 (200 ng/g) and followed until overt diabetes was diagnosed, as defined above. Results IL-22 therapy did not delay the onset of diabetes in comparison with the vehicle-treated mice. We did not observe an improvement in islet area, glycaemic control, beta cell residual function, endoplasmic reticulum stress, insulitis or macrophage and neutrophil infiltration as determined by non-fasting blood glucose, C-peptide and histological scoring. Therapeutic administration of IL-22 did not reduce circulating lipopolysaccharide, a marker of impaired gut mucosal integrity. Conclusions/interpretation Our study suggests that, at this dosing regimen introduced either prior to overt diabetes or at diagnosis of diabetes, recombinant mouse IL-22 therapy cannot prevent autoimmune diabetes, or prolong the honeymoon period in the NOD mouse.