Division of Geriatrics, Xiangya Second Hospital of Central South University, Changsha, Hunan Province, China.
Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Clin Ther. 2019 Mar;41(3):400-409. doi: 10.1016/j.clinthera.2019.02.001. Epub 2019 Mar 1.
The aim was to provide an overview of chronic low-grade inflammatory phenotype (CLIP) and evidence for its role in the pathogenesis of frailty and other chronic conditions as well as potential causative factors and interventions.
We reviewed evidence from published clinical and laboratory studies and summarized the opinions of experts from published reviews.
CLIP is a low-grade, systemic, unresolved, and smoldering chronic inflammatory state clearly indicated by a 2- to 4-fold increase in serum levels of inflammatory mediators, such as interleukin-6 and C-reactive protein. It involves many other cellular and molecular inflammatory mediators. CLIP typically occurs during aging, also known as "inflammaging," and is an integral part of the spectrum of immunosenescence. Causative factors likely include persistent viral infections, particularly chronic cytomegalovirus infection, cellular senescence, failure to eliminate degraded materials and waste products, dysregulated microbiota and gut permeability, obesity, and others. Substantial evidence supports CLIP as a powerful contributing factor to frailty and many other chronic conditions and adverse health outcomes. Many of the inflammatory mediators and their regulatory mechanisms in CLIP may serve as potential targets for therapeutic intervention. However, development of new interventional strategies for CLIP and its associated chronic conditions should take the complexity of the inflammatory network into consideration. Nonpharmacologic interventions, such as caloric restriction and exercise, may have significant impact on CLIP and its causative factors, leading to substantial health benefits. Metformin and resveratrol have anti-inflammatory property and may serve as a promising therapeutic agent for treatment of CLIP and frailty.
CLIP is a chronic inflammatory pathophysiologic process that plays an important role in the pathogenesis of frailty and many other chronic conditions. Improving our understanding of this phenotype may provide opportunities to identify potential targets of effective prevention and therapeutic strategies for frailty and other CLIP-associated conditions.
提供慢性低度炎症表型（CLIP）的概述，并提供其在脆弱和其他慢性疾病发病机制中的作用证据，以及潜在的因果因素和干预措施。
我们综述了已发表的临床和实验室研究证据，并总结了已发表综述中专家的意见。
CLIP 是一种低水平、全身性、未解决的慢性炎症状态，其血清炎症介质（如白细胞介素-6 和 C 反应蛋白）水平升高 2-4 倍即可明确。它涉及许多其他细胞和分子炎症介质。CLIP 通常发生在衰老过程中，也称为“炎症衰老”，是免疫衰老谱的一个组成部分。可能的病因因素包括持续性病毒感染，特别是慢性巨细胞病毒感染、细胞衰老、无法清除降解物质和废物、失调的微生物群和肠道通透性、肥胖等。大量证据表明 CLIP 是脆弱和许多其他慢性疾病及不良健康结局的重要致病因素。CLIP 中的许多炎症介质及其调节机制可能作为治疗干预的潜在靶点。然而，开发针对 CLIP 及其相关慢性疾病的新干预策略时，应考虑到炎症网络的复杂性。非药物干预措施，如热量限制和运动，可能对 CLIP 及其病因因素产生重大影响，带来显著的健康益处。二甲双胍和白藜芦醇具有抗炎作用，可能成为治疗 CLIP 和脆弱的有前途的治疗药物。
CLIP 是一种慢性炎症病理生理过程，在脆弱和许多其他慢性疾病的发病机制中起重要作用。更好地了解这种表型可能为确定脆弱和其他 CLIP 相关疾病的有效预防和治疗策略的潜在靶点提供机会。
