Madihally Sundararajan V, Toner Mehmet, Yarmush Martin L, Mitchell Richard N
Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, Massachusetts 20115, USA.
Ann Surg. 2002 Nov;236(5):649-57. doi: 10.1097/00000658-200211000-00016.
To test the effect of burn injury in mice congenitally deficient in interferon gamma (IFN-gamma) and as well as in wild-type animals treated with IFN-gamma neutralizing antibody.
The mechanisms underlying muscle wasting following burn trauma are incompletely characterized, although the hypercatabolic state is a consequence of increased proteasomal degradation. Concurrently, burn injury results in an immunocompromised state, and subsequent infections are the leading cause of morbidity and mortality in these patients. IFN-gamma, best conceptualized as a macrophage activating protein, modulates a variety of biologic pathways potentially relevant to muscle wasting and immune dysfunction.
Mice received either a 20% total body surface area burn or a control sham treatment. At days 1, 2, and 7 following treatment, skeletal muscle, peripheral blood, and spleen were harvested from both groups. Protein synthesis and degradation rates were measured. Lymphocyte subpopulation expression of major histocompatibility complex I (MHC I) molecules was assessed by flow cytometry, and proliferation capacity was measured using mixed lymphocyte reaction.
IFN-gamma is critically involved in burn-induced weight loss; moreover, absence of IFN-gamma virtually abolished skeletal muscle hypercatabolism following burn injury. Lymphocyte proliferation and MHC I expression in the setting of burn trauma are also normalized in the absence of IFN-gamma. Both antigen presentation and proliferation functions are independently affected.
IFN-gamma plays a fundamental role in mediating the hypercatabolic state of multiple cell types following burn trauma.
检测先天性缺乏γ干扰素（IFN-γ）的小鼠以及用IFN-γ中和抗体处理的野生型动物烧伤后的效果。
烧伤创伤后肌肉萎缩的潜在机制尚未完全明确，尽管分解代谢亢进状态是蛋白酶体降解增加的结果。同时，烧伤会导致免疫功能受损状态，随后的感染是这些患者发病和死亡的主要原因。IFN-γ，最好理解为一种巨噬细胞激活蛋白，可调节多种可能与肌肉萎缩和免疫功能障碍相关的生物学途径。
小鼠接受20%体表面积烧伤或对照假手术治疗。治疗后第1、2和7天，从两组中采集骨骼肌、外周血和脾脏。测量蛋白质合成和降解率。通过流式细胞术评估主要组织相容性复合体I（MHC I）分子的淋巴细胞亚群表达，并使用混合淋巴细胞反应测量增殖能力。
IFN-γ在烧伤引起的体重减轻中起关键作用；此外，缺乏IFN-γ实际上消除了烧伤后骨骼肌的分解代谢亢进。在没有IFN-γ的情况下，烧伤创伤时的淋巴细胞增殖和MHC I表达也恢复正常。抗原呈递和增殖功能均受到独立影响。
IFN-γ在介导烧伤创伤后多种细胞类型的分解代谢亢进状态中起重要作用。
