Animal models, human observational and genetic studies have shown that immune and inflammatory mechanisms play a key role in hypertension and its complications. We review the effects of immunomodulatory interventions on blood pressure, target organ damage and cardiovascular risk in humans. In experimental and small clinical studies both non-specific immunomodulatory approaches, such as mycophenolate mofetil and methotrexate, and medications targeting T and B lymphocytes, such as tacrolimus, cyclosporine, everolimus, rituximab, lower blood pressure and reduce organ damage. Mechanistically targeted immune interventions include isolevuglandin (isoLG) scavengers to prevent neo-antigen formation, co-stimulation blockade (abatacept, belatacept), and anti-cytokine therapies (secukinumab, tocilizumab, canakinumab, TNF-α inhibitors). In many studies, trial designs have been complicated by a lack of blood pressure related endpoints, inclusion of largely normotensive study populations, polypharmacy, and established comorbidities. Among a wide range of interventions reviewed, TNF-α inhibitors have provided the most robust evidence of blood pressure lowering. Treatment of periodontitis also appears to deliver non-pharmacological antihypertensive effects. Evidence of immunomodulatory drugs influencing hypertension-mediated organ damage are discussed. Animal model, observational studies, and trial data in humans support the therapeutic potential of immune targeted therapies in blood pressure lowering and in hypertension-mediated organ damage. Targeted studies are now needed to address their effects on blood pressure in hypertensive individuals.

中文翻译：

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高血压炎症的治疗靶向：从新机制到转化视角

动物模型、人体观察和遗传研究表明，免疫和炎症机制在高血压及其并发症中起着关键作用。我们回顾了免疫调节干预对人类血压、靶器官损伤和心血管风险的影响。在实验和小型临床研究中，非特异性免疫调节方法（例如吗替麦考酚酯和甲氨蝶呤）以及靶向 T 和 B 淋巴细胞的药物（例如他克莫司、环孢菌素、依维莫司、利妥昔单抗）均可降低血压并减少器官损伤。机械靶向免疫干预包括用于防止新抗原形成的异维菌素 (isoLG) 清除剂、共刺激阻断剂（阿巴西普、贝拉西普）和抗细胞因子疗法（苏金单抗、托珠单抗、卡那单抗、TNF-α 抑制剂）。在许多研究中，由于缺乏与血压相关的终点、包括大部分血压正常的研究人群、多种药物治疗和已确定的合并症，试验设计变得复杂。在审查的广泛干预措施中，TNF-α 抑制剂提供了最有力的降压证据。牙周炎的治疗似乎也具有非药物抗高血压作用。讨论了影响高血压介导的器官损伤的免疫调节药物的证据。动物模型、观察性研究和人体试验数据支持免疫靶向疗法在降低血压和高血压介导的器官损伤方面的治疗潜力。现在需要有针对性的研究来解决它们对高血压患者血压的影响。