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Background <p>Type 1 diabetes mellitus (T1DM) is associated with the levels of interleukin-18 (IL-18). However, the effect of exogenous IL-18 and the immune mechanisms involved in this process have not yet been fully elucidated. This study aimed to explore the effects of exogenous IL-18 and immune mechanisms in T1DM.</p> Methods <p>A T1DM mouse model was established using a single intraperitoneal injection of freshly prepared STZ 180&#xa0;mg per body weight. All mice were all separated into three groups, as follows: diabetic mice treated with recombinant IL-18 (1&#xa0;µg/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 evaluate the treatment effect, a linear mixed model was applied. To assess islet morphology and apoptosis, hematoxylin-eosin staining, immunohistochemistry, and immunofluorescence staining (insulin and elevated caspase 3 co-localization) were conducted. Flow cytometry was used to explore immune mechanisms of islet injury.</p> Results <p>The T1DM model was successfully established. During the first 7 days of recombinant IL-18 treatment, the D + IL-18 group of mice were observed to have significantly lower fasting blood glucose levels than the D group of mice (q &lt; 0.012); however, glucose levels were observed to increase thereafter (q &lt; 0.010). The intraperitoneal glucose tolerance test showed a larger area under the curve in the D + IL-18 group than in the D group, suggesting impaired glucose tolerance. Histological evaluation suggested a disruption in islet architecture and a potential increase in elevated caspase 3 expression, which may be indicative of islet dysfunction. Flow cytometry further revealed a trend toward elevated proportions of CD11b⁺F4/80⁺ macrophages and CD3⁻NK1.1⁺ natural killer cells in the pancreas of IL-18-treated mice (<i>p</i> = 0.016).</p> Conclusion <p>Exogenous IL-18 was observed to temporarily ameliorate fasting blood glucose in T1DM mice, but this effect was not sustained beyond day 7, with subsequent impairment of islet function. The latter deterioration may be associated with enhanced infiltration of CD11b⁺F4/80⁺ macrophages and CD3⁻NK1.1⁺ natural killer cells.</p>

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Exploring the effects of exogenous interleukin-18 on islet function and immune mechanisms in type 1 diabetic mice

  • 期刊论文

  • 发表日期：

    2026年5月18日

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  • Mei Xiong,
  • Ting Li,
  • Xian Zhang,
  • Shenggang Ding

摘要

Background

Type 1 diabetes mellitus (T1DM) is associated with the levels of interleukin-18 (IL-18). However, the effect of exogenous IL-18 and the immune mechanisms involved in this process have not yet been fully elucidated. This study aimed to explore the effects of exogenous IL-18 and immune mechanisms in T1DM.

Methods

A T1DM mouse model was established using a single intraperitoneal injection of freshly prepared STZ 180 mg per body weight. All mice were all separated into three groups, as follows: diabetic mice treated with recombinant IL-18 (1 µg/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 evaluate the treatment effect, a linear mixed model was applied. To assess islet morphology and apoptosis, hematoxylin-eosin staining, immunohistochemistry, and immunofluorescence staining (insulin and elevated caspase 3 co-localization) were conducted. Flow cytometry was used to explore immune mechanisms of islet injury.

Results

The T1DM model was successfully established. During the first 7 days of recombinant IL-18 treatment, the D + IL-18 group of mice were observed to have significantly lower fasting blood glucose levels than the D group of mice (q < 0.012); however, glucose levels were observed to increase thereafter (q < 0.010). The intraperitoneal glucose tolerance test showed a larger area under the curve in the D + IL-18 group than in the D group, suggesting impaired glucose tolerance. Histological evaluation suggested a disruption in islet architecture and a potential increase in elevated caspase 3 expression, which may be indicative of islet dysfunction. Flow cytometry further revealed a trend toward elevated proportions of CD11b⁺F4/80⁺ macrophages and CD3⁻NK1.1⁺ natural killer cells in the pancreas of IL-18-treated mice (p = 0.016).

Conclusion

Exogenous IL-18 was observed to temporarily ameliorate fasting blood glucose in T1DM mice, but this effect was not sustained beyond day 7, with subsequent impairment of islet function. The latter deterioration may be associated with enhanced infiltration of CD11b⁺F4/80⁺ macrophages and CD3⁻NK1.1⁺ natural killer cells.