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.