Department of Pathology, Wayne State University, Detroit, MI, United States.
Front Immunol. 2024 Nov 1;15:1460302. doi: 10.3389/fimmu.2024.1460302. eCollection 2024.
Acute inflammation is elicited by lipid and protein mediators in defense of the host following sterile or pathogen-driven injury. A common refrain is that chronic inflammation is a result of incomplete resolution of acute inflammation and behind the etiology of all chronic diseases, including cancer. However, mediators that participate in inflammation are also essential in homeostasis and developmental biology but without eliciting the clinical symptoms of inflammation. This non-inflammatory physiological activity of the so called 'inflammatory' mediators, apparently under the functional balance with anti-inflammatory mediators, is defined as (). Inflammation in the absence of injury is a result of perturbance in due to a decrease in the anti-inflammatory mediators rather than an increase in the inflammatory mediators and leads to chronic inflammation. This concept on the etiology of chronic inflammation suggests that treatment of chronic diseases is better achieved by stimulating the endogenous anti-inflammatory mediators instead of inhibiting the 'inflammatory' mediator biosynthesis with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Furthermore, both 'inflammatory' and anti-inflammatory mediators are present at higher concentrations in the tumor microenvironment compared to normal tissue environments. Since cancer is a proliferative disorder rather than a degenerative disease, it is proposed that heightened , rather than chronic inflammation, drives tumor growth. This understanding helps explain the inefficacy of NSAIDs as anticancer agents. Finally, inhibition of anti-inflammatory mediator biosynthesis in tumor tissues could imbalance toward local acute inflammation triggering an immune response to restore homeostasis and away from tumor growth.
急性炎症是由脂质和蛋白质介质在宿主防御无菌或病原体驱动的损伤时引发的。一个常见的说法是，慢性炎症是急性炎症未完全解决的结果，是所有慢性疾病（包括癌症）的病因。然而，参与炎症的介质在稳态和发育生物学中也是必不可少的，但不会引发炎症的临床症状。这种所谓的“炎症”介质的非炎症生理活性，显然与抗炎介质处于功能平衡状态，被定义为 ()。在没有损伤的情况下发生炎症是由于抗炎介质减少而不是炎症介质增加导致的 失调的结果，从而导致慢性炎症。这种慢性炎症病因的概念表明，通过刺激内源性抗炎介质来治疗慢性疾病比用非甾体抗炎药（NSAIDs）抑制“炎症”介质生物合成的方法更好。此外，“炎症”和抗炎介质在肿瘤微环境中的浓度均高于正常组织环境。由于癌症是一种增殖性疾病，而不是退行性疾病，因此有人提出， 升高而不是慢性炎症，驱动肿瘤生长。这种理解有助于解释 NSAIDs 作为抗癌药物无效的原因。最后，肿瘤组织中抗炎介质生物合成的抑制可能会使 向局部急性炎症失衡，引发免疫反应以恢复稳态，远离肿瘤生长。
