Cachexia is a progressive muscle wasting disease that contributes to death in a wide range of chronic diseases. Currently, the cachexia field lacks animal models that recapitulate the long-term kinetics of clinical disease, which would provide insight into the pathophysiology of chronic cachexia and a tool to test therapeutics for disease reversal. Toxoplasma gondii (T. gondii) is a protozoan parasite that uses conserved mechanisms to infect rodents and human hosts. Infection is lifelong and has been associated with chronic weight loss and muscle atrophy in mice. We have recently shown that T. gondii-induced muscle atrophy meets the clinical definition of cachexia. Here, the longevity of the T. gondii-induced chronic cachexia model revealed that cachectic mice develop perivascular fibrosis in major metabolic organs, including the adipose tissue, skeletal muscle, and liver by 9 weeks post-infection. Development of cachexia, as well as liver and skeletal muscle fibrosis, is dependent on intact signaling through the type I IL-1R receptor. IL-1α is sufficient to activate cultured fibroblasts and primary hepatic stellate cells (myofibroblast precursors in the liver) in vitro, and IL-1α is elevated in the sera and liver of cachectic, suggesting a mechanism by which chronic IL-1R signaling could be leading to cachexia-associated fibrosis.

恶病质是一种进行性肌肉消耗性疾病，可导致多种慢性疾病死亡。目前，恶病质领域缺乏能够概括临床疾病长期动力学的动物模型，这将有助于深入了解慢性恶病质的病理生理学，并提供测试疾病逆转疗法的工具。弓形虫（ T. gondii ）是一种原生动物寄生虫，它利用保守的机制感染啮齿动物和人类宿主。感染是终生的，并且与小鼠的慢性体重减轻和肌肉萎缩有关。我们最近表明弓形虫引起的肌肉萎缩符合恶病质的临床定义。在这里，弓形虫诱导的慢性恶病质模型的寿命表明，恶病质小鼠在感染后 9 周时在主要代谢器官（包括脂肪组织、骨骼肌和肝脏）中出现血管周围纤维化。恶病质以及肝脏和骨骼肌纤维化的发生依赖于 I 型 IL-1R 受体的完整信号传导。 IL-1α足以在体外激活培养的成纤维细胞和原代肝星状细胞（肝脏中的肌成纤维细胞前体），并且IL-1α在恶病质的血清和肝脏中升高，这表明慢性IL-1R信号传导可能通过该机制进行。导致恶病质相关的纤维化。