Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats

• Published in: British journal of cancer Vol. 83; no. 4; pp. 526 - 531
• Main Authors: CARBO, N, LOPEZ-SORIANO, J, COSTELLI, P, BUSQUETS, S, ALVAREZ, B, BACCINO, F. M, QUINN, L. S, LOPEZ-SORIANO, F. J, ARGILES, J. M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.08.2000
• Subjects: Animals; Antineoplastic agents; Apoptosis; Ascites; Biological and medical sciences; Cachexia - drug therapy; Cachexia - etiology; Cachexia - metabolism; Cancer research; Cytokines; Homeostasis; Immunotherapy; Interleukin-15 - pharmacology; Liver Neoplasms, Experimental - complications; Liver Neoplasms, Experimental - metabolism; Male; Medical research; Medical sciences; Metabolism; Muscle Proteins - metabolism; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscular Atrophy - drug therapy; Muscular Atrophy - etiology; Muscular Atrophy - metabolism; Musculoskeletal system; Neoplasm Transplantation; Pharmacology. Drug treatments; Proteins; Rats; Rats, Wistar; Regular; Sarcoma, Yoshida - complications; Sarcoma, Yoshida - metabolism; Space life sciences; Tumor necrosis factor-TNF; Italy; Spain; Antineoplastic agent; Ubiquitin; Animal model; Multicatalytic endopeptidase complex; Rat; Yoshida hepatoma; Hepatic disease; Prevention; Immunotherapy; Turnover; Complication; Malnutrition; Mechanism of action; Nutritional status; Enzyme; Ascites tumor; Cytokine; Rodentia; Metabolic diseases; Cachexia; Malignant tumor; Interleukin 15; Protein; Peptidases; Vertebrata; Mammalia; Treatment; Denutrition; Animal; Digestive diseases; Hydrolases
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1054/bjoc.2000.1299

Tissue protein hypercatabolism (TPH) is an important feature in cancer cachexia, particularly with regard to the skeletal muscle. The Yoshida AH-130 rat ascites hepatoma is a model system for studying the mechanisms involved in the processes that lead to tissue depletion, since it induces in the host a rapid and progressive muscle wasting, primarily due to TPH. The present study was aimed at investigating if IL-15, which is known to favour muscle fibre hypertrophy, could antagonize the enhanced muscle protein breakdown in this cancer cachexia model. Indeed, IL-15 treatment partly inhibited skeletal muscle wasting in AH-130-bearing rats by decreasing (8-fold) protein degradative rates (as measured by 14C-bicarbonate pre-loading of muscle proteins) to values even lower than those observed in non-tumour-bearing animals. These alterations in protein breakdown rates were associated with an inhibition of the ATP-ubiquitin-dependent proteolytic pathway (35% and 41% for 2.4 and 1.2 kb ubiquitin mRNA, and 57% for the C8 proteasome subunit, respectively). The cytokine did not modify the plasma levels of corticosterone and insulin in the tumour hosts. The present data give new insights into the mechanisms by which IL-15 exerts its preventive effect on muscle protein wasting and seem to warrant the implementation of experimental protocols involving the use of the cytokine in the treatment of pathological states characterized by TPH, particularly in skeletal muscle, such as in the present model of cancer cachexia.