Nabisubi Patricia, Mugasa Claire M, Matovu Enock, Ssekatawa Kenneth, Uwituze Vanessa, Ssentamu Geofrey, Namayanja Monica, Kato Charles D
African Center of Excellence in Bioinformatics and Data Intensive Science, the Infectious Disease Institute Makerere University, Kampala, Uganda.
College of Health Science, Makerere University, Kampala, Uganda.
J Exp Pharmacol. 2025 Aug 8;17:545-554. doi: 10.2147/JEP.S529995. eCollection 2025.
Interleukin-6 is a pleiotropic cytokine being explored in therapy for cancer, trauma, and inflammatory infections, albeit with limited data about its safety. The main aim of this study was to investigate the toxicities associated with systemic administration of interleukin-6 in
Four groups of rats, each containing six (6) animals received a daily intramuscular dose of 0.3mls of normal saline, 500ng/kg of recombinant interleukin-6, 1000ng/kg of Interleukin-6, and 2000ng/kg of Interleukin-6 for 21 days. On day 22 post-treatment, rats were euthanized, and blood and body organs were collected for analysis. Blood was used to determine liver and renal function, and hematology parameters, while liver and kidney tissue sections were used for histopathological analysis.
The results revealed that systemic administration of interleukin-6 for 21 days significantly decreased levels of serum creatinine (p<0.00) and serum urea (p<0.01). IL-6 administration had no demonstrable effects on liver function across treatment groups We observed a significant decrease in lymphocytes numbers (p<0.02) across treatment groups when compared to the negative control group. Platelets were significantly elevated in the 100ng/kg treatment groups as compared to the negative control and other treatment groups. Liver and kidney tissue sections for animals that received 500ng/kg of recombinant IL-10 were comparable to those of the negative control and at 1000 and 2000ng/kg, a dose-dependent increase in organ damage was evident.
We demonstrate that systemic administration of recombinant IL-6 at concentrations ranging between 500-1000ng/kg is well tolerated, above this concentration, dose-dependent toxicities and adverse side effects becoming evident. It would be interesting to explore long-term toxicities associated with the systemic administration of IL-6.
白细胞介素-6是一种多效性细胞因子，目前正在癌症、创伤和炎症感染治疗中进行探索，但其安全性数据有限。本研究的主要目的是调查全身给予白细胞介素-6相关的毒性。
四组大鼠，每组六只，每日肌肉注射0.3毫升生理盐水、500纳克/千克重组白细胞介素-6、1000纳克/千克白细胞介素-6和2000纳克/千克白细胞介素-6，持续21天。治疗后第22天，对大鼠实施安乐死，并采集血液和身体器官进行分析。血液用于测定肝功能、肾功能和血液学参数，而肝脏和肾脏组织切片用于组织病理学分析。
结果显示，全身给予白细胞介素-6 21天可显著降低血清肌酐水平（p<0.00）和血清尿素水平（p<0.01）。在各治疗组中，白细胞介素-6给药对肝功能无明显影响。与阴性对照组相比，我们观察到各治疗组淋巴细胞数量显著减少（p<0.02）。与阴性对照组和其他治疗组相比，100纳克/千克治疗组的血小板显著升高。接受500纳克/千克重组白细胞介素-10的动物的肝脏和肾脏组织切片与阴性对照组相当，而在1000和2000纳克/千克时，器官损伤呈剂量依赖性增加。
我们证明，全身给予浓度在500-1000纳克/千克之间的重组白细胞介素-6耐受性良好，高于此浓度，剂量依赖性毒性和不良反应变得明显。探索白细胞介素-6全身给药相关的长期毒性将是一件有趣的事情。
