Nagaraju Santosh, Bertera Suzanne, Funair Amber, Wijkstrom Martin, Trucco Massimo, Cooper David K C, Bottino Rita
Thomas E. Starzl Transplantation Institute; University of Pittsburgh Medical Center ; Pittsburgh , PA USA.
Division of Immunogenetics; Department of Pediatrics; Children's Hospital of Pittsburgh; University of Pittsburgh Medical Center ; Pittsburgh , PA USA.
Islets. 2014;6(3):e944441. doi: 10.4161/19382014.2014.944441.
Streptozotocin (STZ) is used to induce diabetes in experimental animals. It has a variety of adverse effects, ranging from nausea, emesis, and weight loss to liver damage, renal failure, and metabolic acidosis. STZ also has effects on the immune system, being associated with lymphopenia in rodents, the mechanism of which is not fully understood. We present data on a significant STZ-associated reduction in lymphocyte count in nonhuman primates. We report a significant reduction in absolute lymphocyte count; in 2 monkeys, the lymphopenia persisted for >100 d. However, a significant increase in absolute monocyte count was noted. Furthermore, an increase in serum monocyte chemoattractant protein-1 (MCP-1) was observed. The reduction in lymphocyte numbers may contribute to immunomodulation that may be beneficial to a subsequent islet graft, and may reduce the need for immunosuppressive therapy. The increase in monocytes and MCP-1, however, may be detrimental to the islet graft. Studies are warranted to explore the mechanism by which STZ has its effect.
链脲佐菌素(STZ)用于在实验动物中诱导糖尿病。它具有多种不良反应,从恶心、呕吐、体重减轻到肝损伤、肾衰竭和代谢性酸中毒。STZ 对免疫系统也有影响,与啮齿动物的淋巴细胞减少有关,其机制尚未完全了解。我们提供了关于非人类灵长类动物中与 STZ 相关的淋巴细胞计数显著降低的数据。我们报告绝对淋巴细胞计数显著降低;在 2 只猴子中,淋巴细胞减少持续超过 100 天。然而,观察到绝对单核细胞计数显著增加。此外,血清单核细胞趋化蛋白 -1(MCP -1)增加。淋巴细胞数量的减少可能有助于免疫调节,这可能对随后的胰岛移植有益,并可能减少免疫抑制治疗的需求。然而,单核细胞和 MCP -1 的增加可能对胰岛移植有害。有必要开展研究以探索 STZ 发挥作用的机制。