Abstract # 1749 Tumor-induced inflammation mediates behavioral deficits in a murine model of head and neck cancer

Abstract

Patients with cancer often experience fatigue and other symptoms even prior to the start of treatment. Because of the strong association between cancer and inflammation it has been hypothesized that these symptoms are a result of tumor-induced inflammation. We sought to test this hypothesis using a syngeneic heterotopic murine model of human papilloma virus-related head and neck cancer. Mice were implanted or not with 1x106 epithelial tonsil cells transfected with E6/7 of HPV16 and HRAS into the hind leg. The resulting tumor expressed high levels of inflammatory cytokines (e.g., IL-6, IL-1beta, and TNF-alpha) and caused elevated cytokine expression within the liver (i.e., IL-6, IL-1beta, and TNF-alpha) and brain (IL-1beta). The tumor reduced burrowing and voluntary wheel running, but did not induce depression-like behavior. To confirm the existence of low grade inflammation, tumor bearing mice were injected with lipopolysaccharide (0.1 mg/kg, IP). Compared to controls, they showed evidence of priming in the form of increased immobility in the tail suspension task and reduced nest building. Chronic treatment with minocycline attenuated tumor-induced burrowing deficits as well as inflammatory cytokine expression without altering tumor response to chemoradation. These data suggest that the tumor-induced inflammation propagates from the tumor to the liver and brain to induce behavioral alterations that may be effectively targeted through the use of anti-inflammatory interventions.