A Aldabagh Mohammad, Hassoon Ali Kassim, Ibrahim Yahiya Yahiya, H Al-Musawi Mastafa, Ghorbani Marjan
College of Medicine, Medical Research Unit, Al-Nahrain University, Baghdad, Iraq.
Department of Pharmacology & Toxicology, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq.
Immunopharmacol Immunotoxicol. 2025 Feb;47(1):101-111. doi: 10.1080/08923973.2024.2444950. Epub 2025 Jan 6.
Septic shock involves severe systemic inflammatory reaction toward various invading species, such as microorganisms and microbial toxins. Such a response is complicated and characterized as being a dynamic and time-dependent phenomenon. During this response, a significant amount of pro-inflammatory cytokines may be produced, causing a rapid death rate in septic victims and occasionally leading to apoptosis of immune cells within the first hours of septic reaction. In order to ameliorate such septic reaction, intraperitoneal carnosol was studied against lipopolysaccharide (LPS) induced acute inflammatory reaction in Swiss albino mice. An intraperitoneal injection of LPS was performed in Swiss albino mice to induce acute inflammatory reactions. Furthermore, intraperitoneal carnosol was administered alone and in combination with intraperitoneal methyl prednisolone to assess the therapeutic potential of intraperitoneal carnosol against LPS- stimulated acute sepsis. Interferon-gamma, interleukin-4, interleukin-6, interleukin-12, CD28, CD80, CD86, and CTLA-4 were studied as markers of a septic reaction. The current study revealed that intraperitoneal carnosol administration alone and in combination with intraperitoneal methylprednisolone significantly reduced serum levels of interferon-gamma, interleukin-4, interleukin-6, and interleukin-12 serum levels in LPS-induced acute inflammation in mice. Moreover, in the presented study the administration of carnosol via intraperitoneal route produced significant reduction in the serum levels of inflammatory markers. Serum levels of each of CD28, CD86, and CTLA-4 was significantly abolished, while CD80 serum levels was not. In conclusion, accordingly carnosol may offer new therapeutic options to ameliorate acute inflammatory reactions. In addition, combined regimen of both carnosol and methylprednisolone could offer additive anti-inflammatory effects. Moreover, combined carnosol and methylprednisolone therapy may help to permit a reduction in the methylprednisolone dose to reduce the systemic adverse drug reaction toward corticosteroids (methylprednisolone) therapy. Carnosol may offer a therapeutic role in modifying septic inflammatory reactions, suggesting its anti-inflammatory and immunomodulation properties.
脓毒性休克涉及对各种入侵物质（如微生物和微生物毒素）的严重全身炎症反应。这种反应很复杂，其特征是一种动态的、随时间变化的现象。在这种反应过程中，可能会产生大量促炎细胞因子，导致脓毒症患者死亡率迅速上升，偶尔还会在脓毒症反应的最初几个小时内导致免疫细胞凋亡。为了改善这种脓毒症反应，研究了腹腔注射鼠尾草酸对脂多糖（LPS）诱导的瑞士白化小鼠急性炎症反应的影响。在瑞士白化小鼠中进行腹腔注射LPS以诱导急性炎症反应。此外，单独给予腹腔注射鼠尾草酸，并与腹腔注射甲基泼尼松龙联合使用，以评估腹腔注射鼠尾草酸对LPS刺激的急性脓毒症的治疗潜力。研究了γ干扰素、白细胞介素-4、白细胞介素-6、白细胞介素-12、CD28、CD80、CD86和CTLA-4作为脓毒症反应的标志物。目前的研究表明，单独给予腹腔注射鼠尾草酸以及与腹腔注射甲基泼尼松龙联合使用，均可显著降低LPS诱导的小鼠急性炎症中γ干扰素、白细胞介素-4、白细胞介素-6和白细胞介素-12的血清水平。此外，在本研究中，通过腹腔途径给予鼠尾草酸可显著降低炎症标志物的血清水平。CD28、CD86和CTLA-4的血清水平均显著降低，而CD80的血清水平未降低。总之，因此鼠尾草酸可能为改善急性炎症反应提供新的治疗选择。此外，鼠尾草酸和甲基泼尼松龙的联合用药方案可能具有相加的抗炎作用。此外，鼠尾草酸和甲基泼尼松龙联合治疗可能有助于减少甲基泼尼松龙的剂量，以降低对皮质类固醇（甲基泼尼松龙）治疗的全身不良反应。鼠尾草酸可能在调节脓毒症炎症反应中发挥治疗作用，表明其具有抗炎和免疫调节特性。
