Effects of Exogenous Interleukin-18 on Islet Function and Immune Mechanisms in Type 1 Diabetic Mice

Background: Type 1 diabetes mellitus (T1DM) is associated with the levels of interleukin-18 （ IL-18 ）. However, the effect of exogenous IL-18 and immune mechanisms involved have not yet been fully elucidated. This study aimed to inquire into effects of exogenous IL-18 and immune mechanisms in T1DM. Methods : A type 1 diabetes mouse model was established using a single intraperitoneal injection of freshly prepared STZ 180 mg per body weight. All the mice were all separated into three groups: diabetic mice treated with recombinant IL-18 (1 ug/mouse) every other day (D + IL-18 group) ; diabetic mice treated with phosphate-buffered saline (D group); and a control group with non-diabetic mice receiving no treatment. Fasting blood glucose levels were measured throughout the treatment period. At the end of the 10 days treatment, an intraperitoneal glucose tolerance test was performed. To assess islet morphology and apoptosis, hematoxylin-eosin staining, immunohistochemistry, and immunofluorescence staining(insulin and elevate caspase 3 co-localization) were conducted. Flow cytometry was used to explore immune mechanisms of islet injury. Results : The type 1 diabetes mellitus model was successfully established. During the first 7 days of recombinant IL-18 treatment, the D + IL-18 group’s mice showed significantly lower fasting blood glucose levels than the D group’s mice (p < 0.05); however, glucose levels increased thereafter (p < 0.05). The intraperitoneal glucose tolerance test showed a larger area under the curve in the D + IL-18 group than in both the D and control groups (p < 0.05), indicating impaired glucose tolerance. Histological analysis revealed disrupted islet architecture and increased elevate caspase 3 expression, consistent with islet dysfunction. Flow cytometry demonstrated elevated proportions of CD11b⁺F4/80⁺ macrophages and CD3⁻NK1.1⁺ natural killer cells in the pancreas of IL-18–treated mice (p < 0.05). Conclusion : Exogenous IL-18 temporarily ameliorated fasting blood glucose in T1DM mice, followed by deterioration in fasting blood glucose and islets function after day 7 ,potentially due to enhanced infiltration of CD11b⁺F4/80⁺ macrophages and CD3⁻NK1.1⁺ natural killer cells.