UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.
Serviço de Cardiologia, Centro Hospitalar Vila Nova de Gaia/ Espinho, Porto, Portugal.
Inflamm Res. 2022 Aug;71(7-8):771-783. doi: 10.1007/s00011-022-01586-y. Epub 2022 Jun 9.
Inflammation is widely recognized as the driving force of cachexia induced by chronic diseases; however, therapies targeting inflammation do not always reverse cachexia. Thus, whether inflammation per se plays an important role in the clinical course of cachectic patients is still a matter of debate.
To give new insights into cachexia's pathogenesis and diagnosis, we performed a comprehensive literature search on the contribution of inflammatory markers to this syndrome, focusing on the noncommunicable diseases cancer and cardiovascular diseases.
A systematic review was performed in PubMed using the keywords ("cancer" OR "cardiac" cachexia AND "human" OR "patient" AND "plasma" or "serum"). A total of 744 studies were retrieved and, from these, 206 were selected for full-text screening. In the end, 98 papers focusing on circulating biomarkers of cachexia were identified, which resulted in a list of 113 different mediators.
Data collected from the literature highlight the contribution of interleukin-6 (IL-6) and C-reactive protein (CRP) to cachexia, independently of the underlying condition. Despite not being specific, once the diagnosis of cachexia is established, CRP might help to monitor the effectiveness of anti-cachexia therapies. In cardiac diseases, B-type natriuretic peptide (BNP), renin, and obestatin might be putative markers of body wasting, whereas in cancer, growth differentiation factor (GDF) 15, transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF) C seem to be better markers of this syndrome. Independently of the circulating mediators, NF-κB and JAK/STAT signaling pathways play a key role in bridging inflammation with muscle wasting; however, therapies targeting these pathways were not proven effective for all cachectic patients.
The critical and integrative analysis performed herein will certainly feed future research focused on the better comprehension of cachexia pathogenesis toward the improvement of its diagnosis and the development of personalized therapies targeting specific cachexia phenotypes.
炎症被广泛认为是慢性疾病引起恶病质的驱动力；然而，针对炎症的治疗并不总是能逆转恶病质。因此，炎症本身是否在恶病质患者的临床病程中起重要作用仍存在争议。
为了深入了解恶病质的发病机制和诊断，我们对炎症标志物在该综合征中的作用进行了全面的文献检索，重点关注非传染性疾病癌症和心血管疾病。
在 PubMed 上使用关键词（“癌症”或“心脏”恶病质和“人类”或“患者”和“血浆”或“血清”）进行系统综述。共检索到 744 项研究，从中筛选出 206 项进行全文筛选。最终，确定了 98 篇关注恶病质循环生物标志物的论文，这些论文共涉及 113 种不同的介质。
文献中的数据突出了白细胞介素-6（IL-6）和 C 反应蛋白（CRP）对恶病质的贡献，而与潜在疾病无关。尽管 CRP 不具有特异性，但一旦恶病质的诊断确立，它可能有助于监测抗恶病质治疗的效果。在心脏疾病中，B 型利钠肽（BNP）、肾素和肥胖素可能是身体消耗的潜在标志物，而在癌症中，生长分化因子（GDF）15、转化生长因子（TGF）-β1 和血管内皮生长因子（VEGF）C 似乎是该综合征更好的标志物。独立于循环介质，NF-κB 和 JAK/STAT 信号通路在炎症与肌肉消耗之间起着关键的桥梁作用；然而，针对这些通路的治疗方法并不适用于所有恶病质患者。
本文进行的关键和综合分析无疑将为未来的研究提供信息，这些研究将集中于更好地理解恶病质的发病机制，从而改善其诊断和针对特定恶病质表型的个体化治疗的发展。
