title: The effect of altered Toll-like receptor 4 signaling on cancer cachexia.
abstract: OBJECTIVE
  To determine whether mice unable to mount an intact inflammatory response because of a Toll-like receptor (TLR) pathway defect will develop less severe cancer cachexia.
  
  
  METHODS
  Prospective animal study.
  
  
  METHODS
  Academic research center.
  
  
  METHODS
  Six- to eight-week-old, female C3H/HeJ mice (17-18 g) and age-, weight-, and sex-matched wild-type C3H/HeN mice, differing in that the HeJ mice have nonfunctional TLR4 due to a TLR4 double mutation (TLR4(d/d)).
  
  
  METHODS
  The mice were inoculated with equal numbers of SCCF-VII cells and housed in individual cages.
  
  
  METHODS
  Food intake, body weight, pretumor and posttumor body composition, circulating cytokines, and levels of a marker of muscle atrophy were analyzed.
  
  
  RESULTS
  The wild-type HeN mice weighed less on average than the TLR4(d/d) mice (2.6 g vs 4.9 g) (P = .01). They consumed more food, had smaller tumors, and had less lean body mass and fat mass than the TLR4(d/d) mice. Interleukin 1beta level was significantly elevated in the tumor-bearing HeN mice (mean gain of 259 pg/mL) but not in the TLR4(d/d) mice (P = .03). Both mouse strains had evidence of muscle atrophy.
  
  
  CONCLUSIONS
  In spite of increased food intake and smaller tumors, the wild-type HeN mice had more severe cachexia than the TLR4(d/d) mice. The impaired ability to secrete proinflammatory cytokines such as interleukin 1beta may protect these animals from developing severe cancer cachexia. This animal model represents a novel system in which the host contributions to cachexia may be further studied.
authors: Department of Otolaryngology, Head & Neck Surgery, G0412 Neurosciences Hospital, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7070, USA.
authors: Trinitia Y
authors: TY
authors: Cannon
authors: Denis
authors: D
authors: Guttridge
authors: Jason
authors: J
authors: Dahlman
authors: Jonathan R
authors: JR
authors: George
authors: Victor
authors: V
authors: Lai
authors: Carol
authors: C
authors: Shores
authors: Petra
authors: P
authors: Buzková
authors: Marion E
authors: ME
authors: Couch
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001835:Body Weight; D002100:Cachexia / Q000209:etiology / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006258:Head and Neck Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D011446:Prospective Studies; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D051197:Toll-Like Receptor 4