title: Interferon gamma modulates trauma-induced muscle wasting and immune dysfunction.
abstract: 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.
  
  
  BACKGROUND
  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.
authors.affiliation: Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, Massachusetts 20115, USA.
authors.forename: Sundararajan V
authors.initials: SV
authors.lastname: Madihally
authors.forename: Mehmet
authors.initials: M
authors.lastname: Toner
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
authors.forename: Richard N
authors.initials: RN
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D002056:Burns / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006614:Hindlimb; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets; D008214:Lymphocytes / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D015431:Weight Loss / Q000502:physiology*
chemical_list: D011506:Proteins; D007371:Interferon-gamma