Murine interleukin-12 prevents the development of cancer cachexia in a murine model.
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.
Mori
K
K
Department of Oncology, Nippon Roche Research Center, Kamakura City, Japan.
Fujimoto-Ouchi
K
K
Ishikawa
T
T
Sekiguchi
F
F
Ishitsuka
H
H
Tanaka
Y
Y
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000517:prevention & control*; D003110:Colonic Neoplasms / Q000097:blood / Q000150:complications* / Q000628:therapy; D007371:Interferon-gamma / Q000097:blood / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009374:Neoplasms, Experimental
D015850:Interleukin-6; D018664:Interleukin-12; D007371:Interferon-gamma