The effect of altered Toll-like receptor 4 signaling on cancer cachexia.

Conference Paper

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. DESIGN: Prospective animal study. SETTING: Academic research center. SUBJECTS: 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)). INTERVENTION: The mice were inoculated with equal numbers of SCCF-VII cells and housed in individual cages. MAIN OUTCOME MEASURES: 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.

Full Text

Duke Authors

Cited Authors

  • Cannon, TY; Guttridge, D; Dahlman, J; George, JR; Lai, V; Shores, C; Buzková, P; Couch, ME

Published Date

  • December 2007

Published In

Volume / Issue

  • 133 / 12

Start / End Page

  • 1263 - 1269

PubMed ID

  • 18086970

Pubmed Central ID

  • 18086970

International Standard Serial Number (ISSN)

  • 0886-4470

Digital Object Identifier (DOI)

  • 10.1001/archotol.133.12.1263

Conference Location

  • United States