Prolonged Survival of Tumor-bearing Rats with Repetitive Low-Dose Recombinant Tumor Necrosis Factor

摘要: Tumor necrosis factor may be a mediator of the syndrome cancer cachexia. Tachyphylaxis or tolerance to cachectic effects recombinant tumor (rTNF) has been previously described. In this study, we investigate whether repetitive exposure rTNF can induce similar in tumor-bearing (TB) rats and ameliorate cachexia induced by tumor. experiment 1, non-tumor-bearing (NTB) TB were randomized either escalating low doses saline i.p. twice daily for 9 consecutive days. NTB treated with demonstrated significant decline food intake weight change ( P < 0.00001) but soon developed rTNF; they consumed significantly more than on first day treatment had saline. showed 0.0001) also continued treatment. Following treatment, that ate lost less 0.00001). antineoplastic activity, as estimated tumors from controls = 0.003). The anticachexia resulted prolonged survival compared control 0.015). Experiment 2 utilized two different regimens rats: one group received 12 days rTNF, another 15 again greater delayed loss posttreatment was further augmented additional rTNF. Antineoplastic activity clear, overall growth curves not affected Survival increased dose-dependent manner 0.006). Repeated administration induces mild reduction growth, results tumor, prolongation survival.