Skip to main content
The effect of altered Toll-like receptor 4 signaling on cancer cachexia.
- Author(s): Cannon, Trinitia Y;
- Guttridge, Denis;
- Dahlman, Jason;
- George, Jonathan R;
- Lai, Victor;
- Shores, Carol;
- Buzková, Petra;
- Couch, Marion E
- et al.
Published Web Locationhttps://doi.org/10.1001/archotol.133.12.1263
ObjectiveTo 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.
DesignProspective animal study.
SettingAcademic research center.
SubjectsSix- 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)).
InterventionThe mice were inoculated with equal numbers of SCCF-VII cells and housed in individual cages.
Main outcome measuresFood intake, body weight, pretumor and posttumor body composition, circulating cytokines, and levels of a marker of muscle atrophy were analyzed.
ResultsThe 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.
ConclusionsIn 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.
For improved accessibility of PDF content, download the file to your device.