Mechanisms of experimental cancer cachexia. Local involvement of IL-1 in colon-26 tumor.
In the colon-26 (C-26) tumor model, the cytokine IL-6 is an important factor involved in experimental cancer cachexia. Recent in vitro data indicated that IL-1 plays a role in the interaction between host macrophages and C-26 cells that express IL-1R, resulting in the amplification of tumor IL-6 production. To investigate the role of IL-1 on the development of C-26 cachexia in vivo, the effect of specific blockade of the action of IL-1 with reagents against IL-1R was evaluated. Both IL-1R antagonist (IL-1RA) and the mAb 35F5 directed against IL-1R type I, prevented binding of radioactive IL-1, and inhibited IL-1-induced IL-6 synthesis by the C-26 cell line. Whereas a systemic administration of these reagents did not reverse weight loss in C-26-bearing mice, intratumoral injections of IL-1RA significantly reduced cachexia. Furthermore, body composition analysis confirmed that this treatment improved lean tissue and fat, as well as hypoglycemia and serum IL-6 level. The fact that the treatment did not change the tumor burden suggests that it affected the host directly. These results support the hypothesis that, at the microenvironment of the C-26 tumor, IL-1 is involved in the cachexia endured by the host.
Strassmann
G
G
Department of Immunology, Otsuka America Pharmaceutical Inc., Rockville, MD 20850.
Masui
Y
Y
Chizzonite
R
R
Fong
M
M
D000818:Animals; D002100:Cachexia / Q000209:etiology / Q000276:immunology*; D003110:Colonic Neoplasms / Q000150:complications / Q000276:immunology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000150:complications / Q000276:immunology; D012795:Sialoglycoproteins / Q000494:pharmacology
C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins