Zunino S J, Simons L F, Sambrook J F, Gething M J
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas 75235.
Am J Pathol. 1994 Sep;145(3):661-70.
By administering physiological doses of interleukin-1 (IL-1) concurrently with multiple low doses of the beta cell toxin streptozotocin (MSZ), we observed an augmentation of diabetes by IL-1 in four different strains of mice. Augmentation of hyperglycemia by IL-1 was most prominent in the two MSZ-resistant mouse strains Balb/cJ and A/J. Furthermore, concurrent treatment with IL-1 and MSZ rendered these MSZ-resistant mice susceptible to the development of significant insulitis when compared to mice treated with MSZ alone. Development of insulitis was dependent upon the dose of IL-1; it was only observed at an IL-1 dose of 250 ng/kg body weight. Analysis of the leukocytic infiltrate in the islets of mice after treatment with 250 ng/kg IL-1 plus MSZ revealed the presence of L3T4+ and Lyt-2+ T lymphocytes. Administration of MSZ alone or IL-1 alone did not produce diabetes in the MSZ-resistant mice, indicating that neither of these agents was toxic to the beta cells by itself. We conclude that IL-1 synergizes with MSZ to augment diabetes in mice that are normally resistant to the diabetogenic effects of MSZ.
通过将生理剂量的白细胞介素-1（IL-1）与多个低剂量的β细胞毒素链脲佐菌素（MSZ）同时给药，我们观察到在四种不同品系的小鼠中，IL-1增强了糖尿病的发生。在两种对MSZ有抗性的小鼠品系Balb/cJ和A/J中，IL-1对高血糖的增强作用最为显著。此外，与单独用MSZ处理的小鼠相比，IL-1和MSZ联合处理使这些对MSZ有抗性的小鼠易发生显著的胰岛炎。胰岛炎的发生取决于IL-1的剂量；仅在IL-1剂量为250 ng/kg体重时观察到。在用250 ng/kg IL-1加MSZ处理后的小鼠胰岛中白细胞浸润分析显示存在L3T4+和Lyt-2+ T淋巴细胞。单独给予MSZ或单独给予IL-1在对MSZ有抗性的小鼠中均未引发糖尿病，这表明这两种药物单独对β细胞均无毒性。我们得出结论，IL-1与MSZ协同作用，在通常对MSZ致糖尿病作用有抗性的小鼠中增强糖尿病的发生。
