Interleukin-15 is able to suppress the increased DNA fragmentation associated with muscle wasting in tumour-bearing rats.
Administration of interleukin-15 (IL-15) to rats bearing the Yoshida AH-130 ascites hepatoma (a tumour that induces an important cachectic response) resulted in a significant reduction of muscle wasting, both measured as muscle weight and as protein content of different types of skeletal muscle. In addition, the administration of the cytokine completely reversed the increased DNA fragmentation observed in skeletal muscle of tumour-bearing animals. Concerning the mechanism(s) involved in the anti-apoptotic effects of IL-15 on skeletal muscle, the administration of the cytokine resulted in a considerable decrease in both R1 (43%) and R2 (64%) TNF-alpha receptors (TNFRs), and therefore it may be suggested that IL-15 decreases apoptosis by affecting TNF-alpha signalling. Formation of NO could be the signalling event associated with the activation of apoptosis in muscle of tumour-bearing rats; indeed, administration of IL-15 decreased the inducible nitric oxide synthase protein levels by 73%, suggesting that NO formation and muscle apoptosis during tumour growth are related. In conclusion, IL-15 seems to be able to reduce/suppress protein loss and apoptosis related to muscle wasting during cancer cachexia in experimental animals.
Figueras
Maite
M
Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain.
Busquets
Sílvia
S
Carbó
Neus
N
Barreiro
Esther
E
Almendro
Vanessa
V
Argilés
Josep M
JM
López-Soriano
Francisco J
FJ
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006528:Carcinoma, Hepatocellular / Q000503:physiopathology*; D017931:DNA Primers; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019409:Interleukin-15 / Q000627:therapeutic use*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins / Q000627:therapeutic use; D012513:Sarcoma, Experimental / Q000503:physiopathology*
D015703:Antigens, CD; D017931:DNA Primers; D019409:Interleukin-15; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins