Al-Naimi Marwa Salih, Abu-Raghif Ahmed R
Department of Pharmacology, College of Medicine, Al-Nahrain University, Baghdad, Iraq.
Department of Pharmacology and Toxicology, College of Pharmacy, Al-Farahidi University, Baghdad, Iraq.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May;398(5):5845-5865. doi: 10.1007/s00210-024-03659-7. Epub 2024 Nov 30.
Cytokine-releasing syndrome (CRS) is a special form of systemic inflammatory response syndrome provoked by factors like viral infections and certain immunomodulatory drugs like monoclonal antibodies and adoptive T therapy. To elucidate the potential role of ramipril (RM) and its combination with methylprednisolone (MP) against the development and progression of CRS in mice. This experiment consists of two parts: protective and therapeutic interventions. The protective experiment: in the induction group, mice received an intraperitoneal injection (IP) of 5mg/kg lipopolysaccharide (LPS) without intervention. The other groups received various drugs before the induction by three days, then observed for an additional two days (50 mg/kg MP, 3 mg/kg RM, and a combination of 1.5 mg/kg RM with 25 mg/kg MP). The second part of the study involves the therapeutic potential; all groups received similar doses of drugs in the prevention groups, except LPS induction was given first, and after one hour, the mice received daily doses of the drugs for five days. At the end of the experiment, blood and tissue samples were obtained. Mice treated with RM and its combination with MP showed improved serum TNF-α, IL-6, IL-8, IL-1β, INF-γ, MDA, and GSH in both prevention and therapeutic groups. Histopathologically, mice treated with ramipril and its combination with MP ameliorate the tissue damage in both lung and liver tissues following LPS induction. Ramipril showed protective and therapeutic effects in LPS-induced cytokine storms in mice through anti-inflammatory and antioxidant mechanisms.
细胞因子释放综合征（CRS）是一种特殊形式的全身炎症反应综合征，由病毒感染以及某些免疫调节药物（如单克隆抗体和过继性T细胞疗法）等因素引发。为了阐明雷米普利（RM）及其与甲泼尼龙（MP）联合使用对小鼠CRS发生发展的潜在作用。本实验包括两部分：保护性干预和治疗性干预。保护性实验：在诱导组中，小鼠腹腔注射（IP）5mg/kg脂多糖（LPS），不进行干预。其他组在诱导前三天给予各种药物，然后再观察两天（50mg/kg MP、3mg/kg RM以及1.5mg/kg RM与25mg/kg MP的组合）。研究的第二部分涉及治疗潜力；所有组在预防组中接受相似剂量的药物，但先给予LPS诱导，一小时后，小鼠连续五天接受每日剂量的药物。在实验结束时，获取血液和组织样本。在预防组和治疗组中，用RM及其与MP联合治疗的小鼠血清肿瘤坏死因子-α、白细胞介素-6、白细胞介素-8、白细胞介素-1β、干扰素-γ、丙二醛和谷胱甘肽均有所改善。组织病理学上，用雷米普利及其与MP联合治疗的小鼠在LPS诱导后减轻了肺和肝组织的损伤。雷米普利通过抗炎和抗氧化机制对LPS诱导的小鼠细胞因子风暴具有保护和治疗作用。
