Tumor necrosis factor-alpha mediates changes in tissue protein turnover in a rat cancer cachexia model.
Rats bearing the Yoshida AH-130 ascites hepatoma showed enhanced fractional rates of protein degradation in gastrocnemius muscle, heart, and liver, while fractional synthesis rates were similar to those in non-tumor bearing rats. This hypercatabolic pattern was associated with marked perturbations of the hormonal homeostasis and presence of tumor necrosis factor in the circulation. The daily administration of a goat anti-murine TNF IgG to tumor-bearing rats decreased protein degradation rates in skeletal muscle, heart, and liver as compared with tumor-bearing rats receiving a nonimmune goat IgG. The anti-TNF treatment was also effective in attenuating early perturbations in insulin and corticosterone homeostasis. Although these results suggest that tumor necrosis factor plays a significant role in mediating the changes in protein turnover and hormone levels elicited by tumor growth, the inability of such treatment to prevent a reduction in body weight implies that other mediators or tumor-related events were also involved.
Costelli
P
P
Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, Italy.
Carbó
N
N
Tessitore
L
L
Bagby
G J
GJ
Lopez-Soriano
F J
FJ
Argilés
J M
JM
Baccino
F M
FM
D000818:Animals; D002100:Cachexia / Q000378:metabolism*; D007074:Immunoglobulin G / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009132:Muscles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D007074:Immunoglobulin G; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha