Laboratory of Immunoendocrinology, School of Pharmaceutical Sciences, Department of Clinical and Toxicological Analyses, University of São Paulo, São Paulo, SP, Brazil.
Laboratory of Experimental Immunology, Institute of Biomedical Sciences, Department of Immunology, University of São Paulo, São Paulo, SP, Brazil.
Mediators Inflamm. 2021 Oct 19;2021:9940009. doi: 10.1155/2021/9940009. eCollection 2021.
Alloxan (ALX) and streptozotocin (STZ) are extensively used to induce type 1 diabetes (T1D) in animal models. This study is aimed at evaluating the differences in immune parameters caused by ALX and STZ. T1D was induced either with ALX or with STZ, and the animals were followed for up to 180 days. Both ALX and STZ induced a decrease in the total number of circulating leukocytes and lymphocytes, with an increase in granulocytes when compared to control mice (CT). STZ-treated mice also exhibited an increase in neutrophils and a reduction in the lymphocyte percentage in the bone marrow. In addition, while the STZ-treated group showed a decrease in total CD3, CD4CD8, and CD4CD8 T lymphocytes in the thymus and CD19 B lymphocytes in the pancreas and spleen, the ALX group showed an increase in CD4CD8 and CD19 only in the thymus. Basal levels of splenic interleukin- (IL-) 1 and pancreatic IL-6 in the STZ group were decreased. Both diabetic groups showed atrophy of the thymic medulla and degeneration of pancreatic islets of Langerhans composed of inflammatory infiltration and hyperemia with vasodilation. ALX-treated mice showed a decrease in reticuloendothelial cells, enhanced lymphocyte/thymocyte cell death, and increased number of Hassall's corpuscles. Reduced activation of splenic lymphocytes was found in the STZ-treated group. Furthermore, mice immunized with ovalbumin (OVA) showed a more intense antigen-specific paw edema response in the STZ-treated group, while production of anti-OVA IgG1 antibodies was similar in both groups. Thereby, important changes in immune cell parameters and were found at an early stage of T1D in the STZ-treated group, whereas alterations in the ALX-treated group were mostly found in the chronic phase of T1D, including increased mortality rates. These findings suggest that the effects of ALX and STZ influenced, at different times, lymphoid organs and their cell populations.
阿脲（ALX）和链脲佐菌素（STZ）广泛用于诱导动物模型中的 1 型糖尿病（T1D）。本研究旨在评估 ALX 和 STZ 引起的免疫参数差异。通过 ALX 或 STZ 诱导 T1D，动物被随访长达 180 天。与对照小鼠（CT）相比，ALX 和 STZ 均导致循环白细胞和淋巴细胞总数减少，粒细胞增加。STZ 处理的小鼠还表现出中性粒细胞增加和骨髓中淋巴细胞百分比减少。此外，虽然 STZ 处理组在胸腺中显示总 CD3、CD4CD8 和 CD4CD8 T 淋巴细胞以及胰腺和脾脏中的 CD19 B 淋巴细胞减少，但 ALX 组仅在胸腺中显示 CD4CD8 和 CD19 增加。STZ 组脾脏白细胞介素（IL）-1 和胰腺 IL-6 的基础水平降低。两组糖尿病小鼠均表现出胸腺髓质萎缩和胰岛兰格汉斯变性，伴有炎症浸润和血管扩张性充血。ALX 处理的小鼠表现出网状内皮细胞减少、淋巴细胞/胸腺细胞死亡增加和哈索尔氏小体数量增加。STZ 处理组脾淋巴细胞活化减少。此外，用卵清蛋白（OVA）免疫的小鼠在 STZ 处理组中表现出更强烈的抗原特异性爪肿胀反应，而两组的抗 OVA IgG1 抗体产生相似。因此，在 STZ 处理组的 T1D 早期阶段发现免疫细胞参数发生了重要变化，而在 ALX 处理组中，变化主要发生在 T1D 的慢性阶段，包括死亡率增加。这些发现表明，ALX 和 STZ 的作用在不同时间影响了淋巴器官及其细胞群体。
