High interstitial fluid pressure in rat tongue cancer is related to increased lymph vessel area, tumor size, invasiveness and decreased body weight.

BACKGROUND: Interstitial fluid pressure (IFP) in most tumors is high, and this high pressure has been correlated with poor prognosis. Measurements of IFP in normal tongue and in tongue cancer are lacking. Recent research suggests the existence of a relationship between increased peritumoral lymph vessels (PTLV) and survival, and a correlation of increased lymphatic vessel density with an unfavorable prognosis has been reported. MATERIALS AND METHODS: In the present study, tongue squamous cell carcinoma (SCC) was induced by adding the carcinogen 4-nitroquinoline oxide in drinking water for 19 weeks. The IFP was measured by micropuncture and immunohistochemistry was used to visualize lymph vessels. RESULTS: In normal tongue, IFP averaged 3.1 +/- 0.3 mmHg. The IFP, both in the tumor (29.1 +/- 2.9 mmHg) and 0.5 cm anterior to it (15.4 +/- 2.1 mmHg) was consistently increased (P < 0.005) with values ranging from 10 to 40 mmHg. The highest IFP values were measured in rats with large tumors (P < 0.05) and low body weight (P < 0.001), suggesting that IFP increases with cancer progression. Lymphatic vessel area (%), as determined with the lymphatic specific marker LYVE-1 antibody, was significantly increased in the peritumoral area when compared to intratumoral and control mucosa (P < 0.05). There was a significant positive correlation between IFP, PTLV area, tumor size and invasiveness. CONCLUSIONS: Our data show that IFP is increased in tongue cancer. Corresponding changes in PTLV area, invasiveness, tumor area and IFP suggest that the increased pressure is caused by defective lymph drainage and solid stress generated by tumor cells growing in a low compliant environment.

IL-1 alpha and TNF-alpha expression in rat periapical lesions and dental pulp after unilateral sympathectomy.

OBJECTIVES: Apical periodontitis is an inflammatory disease characterized by bone resorption, and sympathetic nerves are known to modulate bone resorption and bone remodeling. Higher numbers of osteoclasts and larger periapical lesions have been observed after sympathectomy in rats, but the mechanisms underlying the inhibitory effect of sympathetic nerves on osteoclasts are unknown. This study aimed to test the hypothesis that sympathetic nerves inhibit the production of the bone-resorbing pro-inflammatory cytokines IL-1 alpha and TNF-alpha in rat periapical lesions. METHODS: Rats were unilaterally sympathectomized and apical lesions were induced by exposing the dental pulp of molar teeth to the oral microflora. We quantified the cytokines IL-1 alpha and TNF-alpha by enzyme-linked immunosorbent assay, and immunohistochemical analysis was done for qualitative localization. Pulp from intact incisor teeth was tested as a control. RESULTS: We showed that IL-1 alpha was increased, but not TNF-alpha, in the periapical lesions on the sympathectomized side. Both IL-1 alpha and TNF-alpha were expressed in unexposed pulp. TNF-alpha was significantly decreased in the denervated incisor pulp, whereas the level of IL-1 alpha remained unchanged. CONCLUSIONS: This study suggests that sympathetic nerves have an inhibitory effect on IL-1 alpha in periapical lesions and a stimulatory effect on TNF-alpha in the intact rat pulp.