Vicovan Andrei Gheorghe, Petrescu Diana Cezarina, Ochiuz Lacramioara, Cianga Petru, Constantinescu Daniela, Iftimi Elena, Pavel-Tanasa Mariana, Ancuta Codrina Mihaela, Caratașu Cezar-Cătălin, Glod Mihai, Solcan Carmen, Ghiciuc Cristina Mihaela
Department of Morpho-Functional Sciences II-Pharmacology and Clinical Pharmacology, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 700115 Iasi, Romania.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania.
Pharmaceuticals (Basel). 2025 Jul 25;18(8):1108. doi: 10.3390/ph18081108.
The study evaluates the immunomodulatory potential of secukinumab (SECU) and honokiol (HONK) in a murine model of allergic asthma complicated by acute lung injury (ALI), with an emphasis on modulating key inflammatory pathways. The rationale is driven by the necessity to attenuate Th17-mediated cytokine cascades, wherein IL-17 plays a critical role, as well as to explore the adjunctive anti-inflammatory effects of HONK on Th1 cytokine production, including IL-6, TNF-α, and Th2 cytokines. Mice were sensitized and challenged with ovalbumin (OVA) and lipopolysaccharide (LPS) was administrated to exacerbate pulmonary pathology, followed by administration of SECU, HONK (98% purity, CHO), or their combination. Quantitative analyses incorporated OVA-specific IgE measurements, differential cell counts in bronchoalveolar lavage fluid (BALF), and extensive cytokine profiling in both BALF and lung tissue homogenates, utilizing precise immunoassays and histopathological scoring systems. Both SECU and HONK, when used alone or in combination, display significant immunomodulatory effects in a murine model of allergic asthma concomitant with ALI. The combined therapy synergistically reduced pro-inflammatory mediators, notably Th1 cytokines, such as TNF-α and IL-6, as measured in both BALF and lung tissue homogenates. The combined therapy showed a synergistic attenuation of pro-inflammatory mediators, a reduction in goblet cell hyperplasia, and an overall improvement in lung histoarchitecture. While the data robustly support the merit of a combinatorial approach targeting multiple inflammatory mediators, the study acknowledges limitations in cytokine diffusion and the murine model's translational fidelity, thereby underscoring the need for further research to optimize clinical protocols for severe respiratory inflammatory disorders.
本研究评估了司库奇尤单抗（SECU）和厚朴酚（HONK）在合并急性肺损伤（ALI）的过敏性哮喘小鼠模型中的免疫调节潜力，重点是调节关键炎症途径。其理论依据是，有必要减弱Th17介导的细胞因子级联反应（其中IL-17起关键作用），以及探索HONK对Th1细胞因子（包括IL-6、TNF-α）和Th2细胞因子产生的辅助抗炎作用。用卵清蛋白（OVA）对小鼠进行致敏和激发，并给予脂多糖（LPS）以加重肺部病变，随后给予SECU、HONK（纯度98%，CHO）或它们的组合。定量分析包括OVA特异性IgE测量、支气管肺泡灌洗液（BALF）中的细胞分类计数，以及利用精确免疫测定和组织病理学评分系统对BALF和肺组织匀浆中的多种细胞因子进行分析。单独使用或联合使用时，SECU和HONK在合并ALI的过敏性哮喘小鼠模型中均显示出显著的免疫调节作用。联合治疗协同降低了促炎介质，尤其是在BALF和肺组织匀浆中检测到的Th1细胞因子，如TNF-α和IL-6。联合治疗显示出对促炎介质的协同减弱、杯状细胞增生的减少以及肺组织结构的整体改善。虽然数据有力地支持了针对多种炎症介质的联合方法的优点，但该研究承认细胞因子扩散和小鼠模型的转化保真度存在局限性，从而强调需要进一步研究以优化严重呼吸道炎症性疾病的临床方案。
