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司库奇尤单抗与厚朴酚用于小鼠急性呼吸道疾病的实验研究

Experimental Insights on the Use of Secukinumab and Magnolol in Acute Respiratory Diseases in Mice.

作者信息

Vicovan Andrei Gheorghe, Petrescu Diana Cezarina, Constantinescu Daniela, Iftimi Elena, Cernescu Irina Teodora, Ancuta Codrina Mihaela, Caratașu Cezar-Cătălin, Șorodoc Laurențiu, Ceasovschih Alexandr, Solcan Carmen, Ghiciuc Cristina Mihaela

机构信息

Department of Morpho-Functional Sciences II-Pharmacology and Clinical Pharmacology, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy of Iași, 16 Universitatii Street, 700115 Iași, Romania.

Department of Immunology, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iași, Romania.

出版信息

Biomedicines. 2024 Jul 11;12(7):1538. doi: 10.3390/biomedicines12071538.

Abstract

This study investigates the combined treatment of secukinumab (SECU) and magnolol (MAGN) in a mouse model of LPS-induced ALI overlapped with allergic pulmonary inflammation, aiming to better understand the mechanism behind this pathology and to assess the therapeutic potential of this novel approach in addressing the severity of ALI. The combined treatment reveals intricate immunomodulatory effects. Both treatments inhibit IL-17 and promote M2 macrophage polarization, which enhances anti-inflammatory cytokine production such as IL-4, IL-5, IL-10, and IL-13, crucial for lung repair and inflammation resolution. However, the combination treatment exacerbates allergic responses and increases OVA-specific IgE, potentially worsening ALI outcomes. MAGN pretreatment alone demonstrates higher potency in reducing neutrophils and enhancing IFN-γ, suggesting its potential in mitigating severe asthma symptoms and modulating immune responses. The study highlights the need for careful consideration in therapeutic applications due to the combination treatment's inability to reduce IL-6 and its potential to exacerbate allergic inflammation. Elevated IL-6 levels correlate with worsened oxygenation and increased mortality in ALI patients, underscoring its critical role in disease severity. These findings offer valuable insights for the advancement of precision medicine within the realm of respiratory illnesses, emphasizing the importance of tailored therapeutic strategies.

摘要

本研究在脂多糖诱导的急性肺损伤(ALI)与过敏性肺部炎症重叠的小鼠模型中,研究了司库奇尤单抗(SECU)和厚朴酚(MAGN)的联合治疗,旨在更好地了解这种病理背后的机制,并评估这种新方法在解决ALI严重程度方面的治疗潜力。联合治疗显示出复杂的免疫调节作用。两种治疗均抑制白细胞介素-17(IL-17)并促进M2巨噬细胞极化,这增强了抗炎细胞因子如IL-4、IL-5、IL-10和IL-13的产生,这些细胞因子对肺修复和炎症消退至关重要。然而,联合治疗会加剧过敏反应并增加卵清蛋白特异性IgE,可能会使ALI的结局恶化。单独使用MAGN预处理在减少中性粒细胞和增强干扰素-γ(IFN-γ)方面显示出更高的效力,表明其在减轻严重哮喘症状和调节免疫反应方面的潜力。该研究强调,由于联合治疗无法降低IL-6且有加剧过敏性炎症的可能性,因此在治疗应用中需要谨慎考虑。IL-6水平升高与ALI患者的氧合恶化和死亡率增加相关,突出了其在疾病严重程度中的关键作用。这些发现为呼吸系统疾病领域的精准医学发展提供了有价值的见解,强调了量身定制治疗策略的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1958/11275060/e19753bb5184/biomedicines-12-01538-g001.jpg

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