Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan, China.
J Transl Med. 2024 Jun 19;22(1):581. doi: 10.1186/s12967-024-05366-6.
Dysregulation of inflammation can lead to multiple chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. Interleukin-6 (IL6) is crucial in regulating the inflammatory cascade, but the causal link between IL6 signaling downregulation and respiratory diseases risk is unclear. This study uses Mendelian randomization to examine the effects of IL6R blockade on respiratory diseases. Analyzing data from 522,681 Europeans, 26 genetic variants were obtained to mimic IL6R inhibition. Our findings show that IL6R blockade significantly reduces the risk of COPD (OR = 0.71, 95% CI = 0.60-9.84) and asthma (OR = 0.82, 95% CI = 0.74-0.90), with protective trends for bronchitis, pulmonary embolism, and lung cancer. Results were consistent across methods, with no significant heterogeneity or pleiotropy. These insights suggest IL6R downregulation as a potential therapeutic target for respiratory diseases, meriting further clinical investigation.
炎症失调可导致多种慢性呼吸道疾病，如慢性阻塞性肺疾病（COPD）和哮喘。白细胞介素 6（IL6）在调节炎症级联反应中至关重要，但 IL6 信号下调与呼吸道疾病风险之间的因果关系尚不清楚。本研究使用孟德尔随机化来研究 IL6R 阻断对呼吸道疾病的影响。分析来自 522681 名欧洲人的数据，获得了 26 个遗传变异来模拟 IL6R 抑制。我们的研究结果表明，IL6R 阻断显著降低 COPD（OR=0.71，95%CI=0.60-9.84）和哮喘（OR=0.82，95%CI=0.74-0.90）的风险，对支气管炎、肺栓塞和肺癌也有保护趋势。结果在各种方法中一致，无显著异质性或多效性。这些结果提示 IL6R 下调可能是呼吸道疾病的潜在治疗靶点，值得进一步临床研究。
