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关键词： 白细胞介素-6   免疫介导的炎症性疾病   细胞因子   靶向治疗   用药管理  

摘要： 免疫介导的炎症性疾病(IMIDs)是一大类由免疫系统异常激活导致的慢性炎症性疾病,其特征是促炎细胞因子过度释放和抗炎调节信号不足的失衡。白细胞介素6(IL-6)是一种多效性细胞因子,因其独特的“三位一体”信号传导机制(经典途径、反式信号传导和反式呈递)而成为连接固有免疫与适应性免疫的“分子桥梁”。IL-6信号通路驱动急性相炎症反应,并以多种机制参与固有免疫的激活及适应性免疫调控,是驱动IMIDs炎症反应、导致多器官损害的关键途径。靶向IL-6通路的药物通过精准阻断IL-6/IL-6受体/gp130信号轴,抑制异常信号传导,为IMIDs治疗带来了革命性突破,广泛用于类风湿关节炎、幼年特发性关节炎/成人斯蒂尔病、巨细胞动脉炎、大动脉炎、Castleman病等多种IMIDs的治疗,目前已上市的药物包括托珠单抗、萨特利珠单抗、萨利鲁单抗和司妥昔单抗。然而,IL-6抑制剂在临床应用中也面临感染风险增加、代谢异常及心血管风险、低纤维蛋白原血症、DRESS综合征等安全性挑战。本综述从分子机制到临床转化,系统阐述了IL-6信号通路的分子机制及其在IMIDs中的致病作用、靶向药物的研发进展及临床应用的安全性问题,旨在促进IL-6靶向治疗从基础到临床的转化,为优化治疗决策提供“机制指导下的个体化”框架,为长期安全性管理体系的建立指明方向。

关键词： 宣肺解毒方   痰热壅肺   头孢唑肟   CAP   IL-6   hs-CRP   TNF-α水平  

摘要： 目的:研究宣肺解毒方联合头孢唑肟治疗痰热壅肺型社区获得性肺炎(community acquired pneumonia,CAP)的疗效及对IL-6、hs-CRP和TNF-α水平的影响。方法:选取平顶山市第一人民医院收治的CAP患者80例,采用随机数字法分成两组,各40例。对照组给予头孢唑肟治疗,治疗组在此基础上给予宣肺解毒方。对比两组治疗后疗效、症状积分、症状消失时间、血清炎性因子水平等。结果:治疗组总有效率明显较高(P<0.05)。治疗组症状消失时间显著较低(P<0.05);两组咳嗽咳痰、痰液黏稠、发热、胸痛评分显著下降(P<0.05);治疗组各症状评分显著低于对照组(P<0.05)。两组患者IL-6、CRP和TNF-α水平显著降低(P<0.05);治疗组白细胞介素(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和C-反应蛋白(C-reactive protein,CRP)水平显著低于对照组(P<0.05)。结论:采用宣肺解毒方联合头孢唑肟治疗CAP,临床疗效较好。

关键词： IV tocilizumab   Macular edema   Subcutaneous tocilizumab   Uveitis   Visual acuity   BCVA   best-corrected visual acuity   CI   confidence interval   DMARD   Disease-modifying anti-rheumatic drug   IL   interleukin   IV   intravenous   logMAR   logarithm of the minimum angle of resolution   TNF   tumor necrosis factor  

摘要：

关键词： extracellular signal‐regulated kinase (ERK)   gastric ulcer (GU)   intercellular adhesion molecule (ICAM)‐1   phosphatidylinositol‐3 kinase (PI3K)   protein kinase B (PKB, AKT)   tumor necrosis factor‐α type 1 receptor (TNFR1)  

摘要： BACKGROUND: About 5%-10% of the world's population is affected by gastric ulcers, which can result in gastrointestinal perforation and bleeding. Consequently, we aimed to investigate whether blocking TNF-α type 1 receptor (TNFR1) with CAY10500 could diminish experimentally induced gastric ulcer (GU) in rats by modulating vascularization. METHODS: Rats were administered with a single oral dose of 80 mg/kg of indomethacin to produce gastric ulcers. Subsequently, some rats were given 1 mg/kg of CAY10500 orally. Gastric samples were used to assess the genetic expression and protein levels of TNFR1, VEGF, ERK, PI3K, AKT (also known as PKB), and ICAM-1. Gastric sections underwent electron microscopic examination and were subjected to hematoxylin and eosin staining and immunostaining using anti-TNFR1, anti-VEGF, and anti-ICAM-1 antibodies. RESULTS: CAY10500 demonstrated the ability to inhibit the expression of TNFR1. Examination of micro-images of GU using electron microscopy or H/E staining revealed extensive necrosis, resulting in the complete loss of regular ultrastructural features of epithelial nuclei and cytoplasmic organelles, as well as the loss of tight junctions and disruption of cell membranes. Significantly, the administration of CAY10500 mitigated these effects. Furthermore, CAY10500 significantly elevated the expressions of VEGF, ERK, PI3K, and AKT, which was associated with a significant reduction in the expression of ICAM-1. CONCLUSION: CAY10500 effectively improved experimentally induced GU in rats. It works by inhibiting TNFR1 and activating angiogenesis and cell proliferation pathways, leading to gastric tissue healing. CAY10500 significantly reduced the adhesion molecule pathways. © 2025 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.

关键词： Canakinumab   Clinical trial failure   Biomarker-driven enrichment  

摘要： Despite compelling preclinical and epidemiological evidence(e.g.,reduced lung cancer incidence in the CANTOS trial),IL-1βinhibition with canakinumab failed to achieve the expected therapeutic effect in the Phase III clinical trials(CANOPY series)of non-small cell lung cancer(NSCLC).This perspective analyzes the disconnect between mechanistic promise and clinical ***-1βdrives NSCLC progression by promoting immunosuppression,angiogenesis,and ***,CANOPY-2 showed no overall survival(OS)benefit,though a trend emerged in patients with an elevated baseline of high-sensitivity C-reactive protein(hs-CRP).Similarly,CANOPY-1 and adjuvant CANOPY-A missed primary endpoints for progression-free survival(PFS)and disease-free survival(DFS),*** failures highlight limitations of IL-1 monotherapy in advanced,immunosuppressive microenvironments and underscore inadequate patient *** propose that IL-1 antagonism retains therapeutic potential but requires refined strategies:biomarker-driven enrichment(e.g.,inflammation signatures like hs-CRP),rational combinatorial regimens informed by successful multi-target agents(e.g.,cadonilimab),and early-stage *** IL-1 blockers through precision approaches could unlock their value in immuno-oncology.

摘要： Neutrophils exert tumor-promoting roles in breast cancer and are particularly prominent in aggressive breast tumors. The proinflammatory signals TGF-$1 and TNF-alpha are upregulated in breast tumors and induce epithelial-to-mesenchymal transitions (EMT), a process linked to cancer cell aggressiveness. Here, we investigated the roles of TGF-$1 and TNF-alpha in the recruitment of neutrophils by breast cancer cells. Dual-treatment with TGF-$1 and TNF-alpha induces EMT signatures in premalignant M2 cells, which are part of the MCF10A breast cancer progression model. Conditioned media (CM) harvested from M2 cells treated with TGF-$1/TNF-alpha gives rise to amplified neutrophil chemotaxis compared with CM from vehicle-treated M2 cells. This response correlates with higher levels of the neutrophil chemokines CXCL1 and CXCL8, in a p38MAPK-dependent manner, and is attenuated by CXCL8-neutralizing antibodies. We combined gene editing, immunological, and biochemical assays to show that neutrophil recruitment and EMT are uncoupled in treated M2 cells. Finally, analysis of transcriptomic databases of cancer cell lines revealed a significant correlation between CXCL8 and TGF-$1/TNF-alpha-regulated or effector genes in breast cancer. These findings establish a novel role for the TGF-$1/TNF-alpha/p38 MAPK signaling axis in regulating neutrophil recruitment in breast cancer, independent of their profound impact on EMT.

关键词： 晚期结直肠癌   淋巴细胞亚群   细胞因子   免疫治疗   预测价值  

摘要： 目的评估淋巴细胞亚群及细胞因子在预测晚期结直肠癌患者免疫治疗效果中的作用,以期为晚期结直肠癌患者的个体化治疗提供有效的临床预测工具。方法收集江苏省苏州市立医院2022年10月至2025年4月收治的接受程序性细胞死亡受体1/程序性细胞死亡受体配体1抑制剂治疗的52例晚期结直肠癌患者的临床资料进行回顾性分析。根据实体瘤疗效评价标准分为完全缓解、部分缓解、疾病稳定和疾病进展,其中完全缓解、部分缓解、疾病稳定患者归入控制组(29例),疾病进展患者归入进展组(23例)。比较2组治疗前后淋巴细胞亚群(调节性T细胞、CD_(3)^(+)、CD_(4)^(+)、CD_(8)^(+)、CD+19、自然杀伤细胞)和细胞因子[白细胞介素2(IL-2)、IL-4、IL-6、IL-10、肿瘤坏死因子α、γ干扰素]的水平,分析其与免疫治疗效果的相关性。结果治疗前控制组自然杀伤细胞水平显著高于进展组[19.1%(14.6%,24.9%)比8.0%(7.2%,18.2%)](P=0.041)。治疗后进展组IL-6显著高于治疗前,控制组显著低于治疗前,控制组低于进展组[4.7(3.5,9.5)ng/L比17.3(14.7,47.4)ng/L],差异有统计学意义(均P<0.05)。通过Pearson相关性分析发现,IL-6与肿瘤进展呈负相关关系(r=-0.489,P=0.003),提示IL-6水平越高,治疗效果越差。结论自然杀伤细胞和IL-6在预测晚期结直肠癌患者免疫治疗效果中具有潜在价值。自然杀伤细胞水平的升高与更好的治疗反应相关,而IL-6的升高则可能预示较差的预后。

关键词： 骨细胞   骨衰老   免疫微环境   免疫细胞   细胞因子   免疫衰老   免疫治疗   工程化组织构建  

摘要： 背景:骨骼微环境中富含各种免疫细胞和细胞因子,它们与骨细胞紧密联系形成了相互影响的网络,因此,骨骼的衰老不单单是由骨细胞衰老导致,免疫系统衰老同样会加速骨衰老过程。目的:综述骨髓间充质干细胞、成骨细胞和破骨细胞以及骨微环境中免疫细胞的年龄相关变化,强调免疫微环境在骨衰老中的关键作用以及免疫治疗在骨衰老治疗中的潜力。方法:检索PubMed数据库、中国知网中关于骨骼细胞衰老与免疫细胞衰老相互作用的文献,英文检索词为“Osteocytes,Bone aging,Immune microenvironment,Immune cells,Cytokines,Immunosenescence,Immunotherapy”,中文检索词为“骨细胞,骨衰老,免疫微环境,免疫细胞,细胞因子,免疫衰老,免疫治疗”。根据纳入与排除标准,最终纳入128篇文献进行综述。结果与结论:骨衰老是老年人普遍存在的一种病理状态,以多种生物学过程相互作用为特征,其中免疫因素起着关键作用。免疫微环境中的细胞、分子和信号通路共同构成了一个复杂的网络,这个网络的失衡会加速骨衰老进程。抗细胞衰老与免疫治疗相结合可能为骨衰老疾病的治疗带来新的方法,包括清除衰老的细胞、衰老相关分泌表型靶向药物、炎症细胞因子靶向治疗、免疫细胞调节疗法、干细胞治疗及分子治疗等。为了更有效且合理地清除衰老细胞,需要更深入地了解衰老细胞的机制,这将有助于更准确地识别衰老细胞。免疫治疗在骨衰老治疗中展现出强大的潜力和前途,但存在一些潜在的风险。相信随着科技的进步,人们可以更准确地了解人体的遗传信息和免疫状态,制定更个性化的免疫治疗方案。

关键词： 妊娠期高血压疾病   胎儿宫内缺氧   高迁移率族蛋白B1   白细胞介素-37   纤维蛋白原  

摘要： 目的探讨血清高迁移率族蛋白B1(HMGB1)、白细胞介素-37(IL-37)对妊娠期高血压疾病(HDP)孕妇发生胎儿宫内缺氧的预测价值。方法选取2022年1月至2024年1月四川省达州市妇女儿童医院收治的100例HDP孕妇作为研究组,根据胎儿宫内缺氧发生情况将HDP孕妇分为正常组和宫内缺氧组。另选取同期在四川省达州市妇女儿童医院产前检查正常且无合并症的100例健康孕妇作为对照组。采用酶联免疫吸附试验检测所有研究对象血清HMGB1、IL-37水平。采用多因素Logistic回归分析HDP孕妇发生胎儿宫内缺氧的影响因素。采用受试者工作特征(ROC)曲线分析血清HMGB1、IL-37对HDP孕妇发生胎儿宫内缺氧的预测价值。结果研究组血清HMGB1水平明显高于对照组,血清IL-37水平明显低于对照组,差异均有统计学意义(P<0.05)。宫内缺氧组血清HMGB1、纤维蛋白原(FIB)水平均明显高于正常组,血清IL-37水平明显低于正常组,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,血清HMGB1、FIB水平升高均为HDP孕妇发生胎儿宫内缺氧的危险因素(P<0.05),血清IL-37水平升高为HDP孕妇发生胎儿宫内缺氧的保护因素(P<0.05)。ROC曲线分析结果显示,血清HMGB1、IL-37二者联合预测HDP孕妇发生胎儿宫内缺氧的曲线下面积(AUC)为0.932,大于二者单独预测的AUC(0.853、0.838),差异均有统计学意义(Z=2.068、2.545,P=0.039、0.011)。结论发生胎儿宫内缺氧的HDP孕妇血清HMGB1水平升高,血清IL-37水平降低,二者均是HDP孕妇发生胎儿宫内缺氧的影响因素,且二者联合预测HDP孕妇发生胎儿宫内缺氧的价值更高。