Institute of Cardiovascular Physiology and Pathophysiology, Walter Brendel Center of Experimental Medicine, University Hospital, Ludwig-Maximilian University, Großhaderner Str. 9, Planegg-Martinsried, 82152, Munich, Germany.
Department of Dermatology and Allergy, School of Medicine, Technical University of Munich, Munich, Germany.
Intern Emerg Med. 2023 Sep;18(6):1647-1664. doi: 10.1007/s11739-023-03309-5. Epub 2023 May 30.
Mounting experimental evidence from in vitro and in vivo animal studies points to an essential role of the CXCL8-CXCR1/2 axis in neutrophils in the pathophysiology of inflammatory and autoimmune diseases. In addition, the pathogenetic involvement of neutrophils and the CXCL8-CXCR1/2 axis in cancer progression and metastasis is increasingly recognized. Consequently, therapeutic targeting of CXCR1/2 or CXCL8 has been intensively investigated in recent years using a wide array of in vitro and animal disease models. While a significant benefit for patients with unwanted neutrophil-mediated inflammatory conditions may be expected from a potential clinical use of inhibitors, their use in severe infections or sepsis might be problematic and should be carefully and thoroughly evaluated in animal models and clinical trials. Translating the approaches using inhibitors of the CXCL8-CXCR1/2 axis to cancer therapy is definitively a new and promising research avenue, which parallels the ongoing efforts to clearly define the involvement of neutrophils and the CXCL8-CXCR1/2 axis in neoplastic diseases. Our narrative review summarizes the current literature on the activation and inhibition of these receptors in neutrophils, key inhibitor classes for CXCR2 and the therapeutic relevance of CXCR2 inhibition focusing here on gastrointestinal diseases.
越来越多的证据表明，在体外和体内动物研究中，CXCL8-CXCR1/2 轴在中性粒细胞中的作用对于炎症和自身免疫性疾病的病理生理学至关重要。此外，中性粒细胞和 CXCL8-CXCR1/2 轴在癌症进展和转移中的发病机制也越来越受到重视。因此，近年来，人们利用各种体外和动物疾病模型，对 CXCR1/2 或 CXCL8 的治疗靶向进行了深入研究。虽然抑制物的潜在临床应用可能会使患有不受控制的中性粒细胞介导的炎症疾病的患者受益，但在严重感染或败血症中使用这些抑制剂可能会出现问题，并且应该在动物模型和临床试验中仔细和彻底地进行评估。将抑制 CXCL8-CXCR1/2 轴的方法转化为癌症治疗方法无疑是一个新的、有前途的研究方向，这与正在努力明确中性粒细胞和 CXCL8-CXCR1/2 轴在肿瘤疾病中的作用是平行的。我们的叙述性综述总结了目前关于中性粒细胞中这些受体的激活和抑制的文献，重点介绍了 CXCR2 的关键抑制剂类别和 CXCR2 抑制的治疗相关性，这里主要关注胃肠道疾病。
