Immunomodulatory interventions in myocardial infarction and heart failure: a systematic review of clinical trials and meta-analysis of IL-1 inhibition.
Immunomodulatory interventions in myocardial infarction and heart failure: a systematic review of clinical trials and meta-analysis of IL-1 inhibition.
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DOI：
10.1093/cvr/cvy145
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发表时间：
2018-09-01
影响因子：
10.8
通讯作者：
Sattler S
中科院分区：
文献类型：
--
作者：
Panahi M;Papanikolaou A;Torabi A;Zhang JG;Khan H;Vazir A;Hasham MG;Cleland JGF;Rosenthal NA;Harding SE;Sattler S
心肌梗死（MI）后，免疫系统有助于修复缺血性损伤和恢复组织完整性，但过度炎症与不良心脏重塑和心力衰竭（HF）的发展有关。临床前研究表明，及时解决炎症可能有助于预防HF的发展和进展。预防患者过度MI后炎症的治疗尝试包括从广泛的免疫抑制到靶向特定细胞类型或因子的免疫调节方法的药理学干预，目的是维持MI后早期免疫应答的有益方面。这些包括阻断炎症的早期引发剂，包括活性氧和补体，抑制肥大细胞脱粒和白细胞浸润，阻断炎性细胞因子，以及抑制适应性B和T淋巴细胞。在此，我们对心肌梗死后免疫调节试验进行了系统综述，并对针对炎症细胞因子白细胞介素-1的研究进行了荟萃分析。尽管大量的临床试验对各种目标进行了巨大的努力，但研究人群、治疗时间和类型以及高度可变的终点的显著异质性限制了有意义的荟萃分析的可能性。总之，我们强调了未来研究的关键考虑因素，包括（i）治疗的机会窗口，（ii）常规MI后药物的免疫学效应，（iii）高度多样化的MI后患者人群的分层，（iv）免疫调节与再生治疗相结合的潜在益处，以及最后（v）免疫治疗的潜在副作用。
Following a myocardial infarction (MI), the immune system helps to repair ischaemic damage and restore tissue integrity, but excessive inflammation has been implicated in adverse cardiac remodelling and development towards heart failure (HF). Pre-clinical studies suggest that timely resolution of inflammation may help prevent HF development and progression. Therapeutic attempts to prevent excessive post-MI inflammation in patients have included pharmacological interventions ranging from broad immunosuppression to immunomodulatory approaches targeting specific cell types or factors with the aim to maintain beneficial aspects of the early post-MI immune response. These include the blockade of early initiators of inflammation including reactive oxygen species and complement, inhibition of mast cell degranulation and leucocyte infiltration, blockade of inflammatory cytokines, and inhibition of adaptive B and T-lymphocytes. Herein, we provide a systematic review on post-MI immunomodulation trials and a meta-analysis of studies targeting the inflammatory cytokine Interleukin-1. Despite an enormous effort into a significant number of clinical trials on a variety of targets, a striking heterogeneity in study population, timing and type of treatment, and highly variable endpoints limits the possibility for meaningful meta-analyses. To conclude, we highlight critical considerations for future studies including (i) the therapeutic window of opportunity, (ii) immunological effects of routine post-MI medication, (iii) stratification of the highly diverse post-MI patient population, (iv) the potential benefits of combining immunomodulatory with regenerative therapies, and at last (v) the potential side effects of immunotherapies.
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影响因子：
20.1
作者：
Frangogiannis NG
通讯作者：
Frangogiannis NG
影响因子：
37.8
作者：
ARSTALL, MA;YANG, JF;HOROWITZ, JD
通讯作者：
HOROWITZ, JD
影响因子：
37.8
作者：
Fukushima, Satsuki;Coppen, Steven R.;Suzuki, Ken
通讯作者：
Suzuki, Ken
影响因子：
4.8
作者：
Fahmi A;Smart N;Punn A;Jabr R;Marber M;Heads R
通讯作者：
Heads R
影响因子：
4
作者：
Carroll, Matthew B.;Haller, Charles;Smith, Christopher
通讯作者：
Smith, Christopher