MURINE INTERLEUKIN-12 PREVENTS THE DEVELOPMENT OF CANCER CACHEXIA IN A MURINE MODEL

Murine colon 26 carcinoma causes cachexia even when the tumor burden i s small. In this tumor model, murine IL-12 suppressed the induction of cancer cachexia and also inhibited tumor growth. IL-12 reduced the se rum 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 ac tivity was observed even at low doses of IL-12, insufficient to inhibi t tumor growth. IL-12 greatly increased levels of IFN-gamma in the tum or 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 athy mic mice bearing the same colon 26 tumor, IL-12 was no longer anticach ectic and did not induce IFN-gamma. These results indicate that the an ticachectic 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.