Prevention of adenocarcinoma colon 26-induced cachexia by interleukin 10 gene transfer

• Published in: Cancer research (Chicago, Ill.) Ill.), 1997, Vol.57 (1), p.94-99
• Main Authors: FUJIKI, F, MUKAIDA, N, MATSUSHIMA, K, HIROSE, K, ISHIDA, H, HARADA, A, OHNO, S, BLUETHMANN, H, KAWAKAMI, M, AKIYAMA, M, SONE, S
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Cachexia - genetics; Cachexia - metabolism; Cachexia - prevention & control; Colonic Neoplasms - complications; Colonic Neoplasms - metabolism; Female; Immunotherapy; Interferon-gamma - metabolism; Interleukin-1 - metabolism; Interleukin-10 - genetics; Interleukin-10 - metabolism; Interleukin-10 - physiology; Interleukin-6 - deficiency; Interleukin-6 - metabolism; Medical sciences; Mice; Mice, Inbred BALB C; Neoplasms, Experimental - complications; Neoplasms, Experimental - metabolism; Pharmacology. Drug treatments; RNA, Messenger - metabolism; Specific Pathogen-Free Organisms; Transfection; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0008-5472; 1538-7445

A s.c. injection of a mouse colon adenocarcinoma cell line, colon 26 clone 20, induced cachexia, as evidenced by progressive weight loss and severe hypoglycemia. Several lines of evidence indicate that a pro-inflammatory cytokine, interleukin 6 (IL-6), plays a major role, albeit partially, in the establishment of cachexia in this model. Because IL-10 can potentially inhibit the production of pro-inflammatory cytokines including IL-6, we evaluated the effects of IL-10 gene transfer on the establishment of cachexia. IL-6 transcript was detected at tumor sites of mice inoculated with parental or control vector transfectant cells, and serum IL-6 levels were markedly increased in these mice. The injection of parental cells into IL-6-deficient mice induced cachexia with elevated serum IL-6 levels comparable to wild-type mice, indicating that tumor cells are a major source of IL-6. The inoculation of IL-10-transfectant cells kept IL-10 mRNA expression at tumor sites and induced the elevation in serum IL-10 levels without affecting the growth rates of colon 26 cells both in vitro and in vivo. However, the implantation with IL-10-transfectant cells reduced the expression of IL-6 mRNA at the tumor sites and the elevation in serum IL-6 levels. Concomitantly, mice inoculated with IL-10-transfectant cells did not exhibit progressive weight loss, a reduction in food intake, or severe hypoglycemia, which was observed in mice inoculated with parental or control vector-transfectant cells. Collectively, these results suggest that IL-10 gene transfer prevented the occurrence of cachexia with a concomitant inhibition of IL-6 production at the tumor sites.