Interferon gamma modulates trauma-induced muscle wasting and immune dysfunction

被引:29
作者
Madihally, SV
Toner, M
Yarmush, ML
Mitchell, RN
机构
[1] Brigham & Womens Hosp, Dept Pathol, Div Immunol, Boston, MA 02115 USA
[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Surg Serv, Boston, MA USA
[3] Shriners Hosp Children, Boston, MA USA
关键词
D O I
10.1097/00000658-200211000-00016
中图分类号
R61 [外科手术学];
学科分类号
摘要
Objective 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. Summary Background Data 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. Methods 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. Results 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. Conclusions IFN-gamma plays a fundamental role in mediating the hypercatabolic state of multiple cell types following burn trauma.
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页码:649 / 657
页数:9
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