Department of Bionano Engineering, Hanyang University, Seoul, Republic of Korea.
Center for Bionano Intelligence Education and Research, Hanyang University, Ansan, Republic of Korea.
Front Immunol. 2024 Jul 16;15:1424768. doi: 10.3389/fimmu.2024.1424768. eCollection 2024.
Conditions such as acute pancreatitis, ulcerative colitis, delayed graft function and infections caused by a variety of microorganisms, including gram-positive and gram-negative organisms, increase the risk of sepsis and therefore mortality. Immune dysfunction is a characterization of sepsis, so timely and effective treatment strategies are needed. The conventional approaches, such as antibiotic-based treatments, face challenges such as antibiotic resistance, and cytokine-based treatments have shown limited efficacy. To address these limitations, a novel approach focusing on membrane receptors, the initiators of the inflammatory cascade, is proposed. Membrane receptors such as Toll-like receptors, interleukin-1 receptor, endothelial protein C receptor, μ-opioid receptor, triggering receptor expressed on myeloid cells 1, and G-protein coupled receptors play pivotal roles in the inflammatory response, offering opportunities for rapid regulation. Various membrane receptor blockade strategies have demonstrated efficacy in both preclinical and clinical studies. These membrane receptor blockades act as early stage inflammation modulators, providing faster responses compared to conventional therapies. Importantly, these blockers exhibit immunomodulatory capabilities without inducing complete immunosuppression. Finally, this review underscores the critical need for early intervention in acute inflammatory and infectious diseases, particularly those posing a risk of progressing to sepsis. And, exploring membrane receptor blockade as an adjunctive treatment for acute inflammatory and infectious diseases presents a promising avenue. These novel approaches, when combined with antibiotics, have the potential to enhance patient outcomes, particularly in conditions prone to sepsis, while minimizing risks associated with antibiotic resistance and immune suppression.
急性胰腺炎、溃疡性结肠炎、移植物功能延迟和各种微生物(包括革兰氏阳性和革兰氏阴性菌)引起的感染等情况会增加脓毒症的风险,从而导致死亡率升高。免疫功能障碍是脓毒症的特征,因此需要及时有效的治疗策略。传统的方法,如基于抗生素的治疗,面临着抗生素耐药性等挑战,而基于细胞因子的治疗已显示出有限的疗效。为了解决这些限制,提出了一种针对膜受体的新方法,膜受体是炎症级联反应的启动者。Toll 样受体、白细胞介素-1 受体、内皮蛋白 C 受体、μ-阿片受体、髓样细胞表达的触发受体 1 和 G 蛋白偶联受体等膜受体在炎症反应中发挥着关键作用,为快速调节提供了机会。各种膜受体阻断策略在临床前和临床研究中都显示出了疗效。这些膜受体阻断剂作为早期炎症调节剂,与传统疗法相比,具有更快的反应速度。重要的是,这些阻滞剂具有免疫调节能力,而不会引起完全的免疫抑制。最后,这篇综述强调了早期干预急性炎症和感染性疾病的迫切需要,特别是那些有进展为脓毒症风险的疾病。探索膜受体阻断作为急性炎症和感染性疾病的辅助治疗方法具有广阔的前景。这些新方法与抗生素联合使用,有可能改善患者的预后,特别是在易发生脓毒症的情况下,同时最大限度地降低抗生素耐药性和免疫抑制相关的风险。