Mori K, Fujimoto-Ouchi K, Ishikawa T, Sekiguchi F, Ishitsuka H, Tanaka Y
Department of Oncology, Nippon Roche Research Center, Kamakura City, Japan.
Int J Cancer. 1996 Sep 17;67(6):849-55. doi: 10.1002/(SICI)1097-0215(19960917)67:6<849::AID-IJC15>3.0.CO;2-X.
Murine colon 26 carcinoma causes cachexia even when the tumor burden is small. In this tumor model, murine IL-12 suppressed the induction of cancer cachexia and also inhibited tumor growth. IL-12 reduced the serum levels of IL-6, a cachexia mediator in this model, and alleviated the body weight loss and other abnormalities associated with cachexia, such as adipose tissue wasting and hypoglycemia. The anticachectic activity was observed even at low doses of IL-12, insufficient to inhibit tumor growth. IL-12 greatly increased levels of IFN-gamma in the tumor tissue and, to a lesser extent, in the circulation. IFN-gamma given intraperitoneally also prevented cancer cachexia, although it did not reduce IL-6 levels either in the tumor or in the circulation. In athymic mice bearing the same colon 26 tumor, IL-12 was no longer anticachectic and did not induce IFN-gamma. These results indicate that the anticachectic activity of IL-12 is T-cell-dependent and results from at least 2 mechanisms, the down-regulation of IL-6 and the up-regulation of IFN-gamma.
即使肿瘤负荷较小，小鼠结肠26癌也会导致恶病质。在这个肿瘤模型中，小鼠白细胞介素-12（IL-12）抑制了癌症恶病质的诱导，并且还抑制了肿瘤生长。IL-12降低了该模型中作为恶病质介质的白细胞介素-6（IL-6）的血清水平，并减轻了体重减轻以及与恶病质相关的其他异常情况，如脂肪组织消耗和低血糖。即使在低剂量的IL-12下也观察到了抗恶病质活性，该剂量不足以抑制肿瘤生长。IL-12极大地提高了肿瘤组织中γ干扰素（IFN-γ）的水平，在较小程度上也提高了循环中的水平。腹腔注射IFN-γ也可预防癌症恶病质，尽管它并未降低肿瘤或循环中的IL-6水平。在携带相同结肠26肿瘤的无胸腺小鼠中，IL-12不再具有抗恶病质作用，也不诱导IFN-γ。这些结果表明，IL-12的抗恶病质活性是T细胞依赖性的，并且至少由两种机制导致，即IL-6的下调和IFN-γ的上调。
