In vivo gene transfer of murine interleukin-4 inhibits colon-26-mediated cancer cachexia in mice.
Cancer cachexia has been suggested to be mediated by various cytokines derived either from tumor or host tissue. In the murine colon-26 (C-26) adenocarcinoma model IL-1, secreted by tumor-infiltrating mononuclear phagocytes, has an important role in induction of cancer cachexia. In order to suppress production of IL-1 in peritoneal macrophages we have used liposome-mediated gene transfer of the anti-inflammatory cytokine mIL-4, known as a potent inhibitor of IL-1 production. Balb/c mice were transfected by intraperitoneal inoculation of C-26 tumor cells. The mIL-4 transfected animals showed increased survival rate, delayed symptoms of cachexia and reduced anorexia in comparison with tumor-bearing control groups. However, tumor growth inhibition was not seen in mIL-4-transfected animals. Peritoneal macrophages from surviving mIL-4-transfected mice, when stimulated with LPS ex vivo, showed decreased IL-1 alpha production, 1672 +/- 202 pg/2 x 10(6) cells in contrast to tumor-bearing control animals, 3975 +/- 89 pg/2 x 10(6) cells, mock-transfected tumor-bearing animals 4004 +/- 174 pg/2 x 10(6) cells and tumor-free animals, 3142 +/- 60 pg/2 x 10(6) cells (p < 0.004). The present study demonstrates that in vivo gene transfer of an anti-inflammatory cytokine reduces cancer-associated cachexia by inhibition of IL-1 alpha production of tumor surrounding peritoneal macrophages, without a significant effect on tumor growth.
Sturlan
Sanda
S
Department of General Surgery, University of Vienna, Vienna, Austria.
Beinhauer
Britta G
BG
Oberhuber
Georg
G
Huang
Leaf
L
Aasen
Ansgar O
AO
Rogy
Michael A
MA
D000230:Adenocarcinoma / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002100:Cachexia / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D003110:Colonic Neoplasms / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics*; D008081:Liposomes / Q000008:administration & dosage; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection
D007375:Interleukin-1; D008081:Liposomes; D015847:Interleukin-4