Interleukin 6 receptor antibody inhibits muscle atrophy and modulates proteolytic systems in interleukin 6 transgenic mice.
The muscles of IL-6 transgenic mice suffer from atrophy. Experiments were carried out on these transgenic mice to elucidate activation of proteolytic systems in the gastrocnemius muscles and blockage of this activation by treatment with the anti-mouse IL-6 receptor (mIL-6R) antibody. Muscle atrophy observed in 16-wk-old transgenic mice was completely blocked by treatment with the mIL-6R antibody. In association with muscle atrophy, enzymatic activities and mRNA levels of cathepsins (B and L) and mRNA levels of ubiquitins (poly- and mono-ubiquitins) increased, whereas the mRNA level of muscle-specific calpain (calpain 3) decreased. All these changes were completely eliminated by treatment with the mIL-6R antibody. This IL-6 receptor antibody could, therefore, be effective against muscle wasting in sepsis and cancer cachexia, where IL-6 plays an important role.
Department of Surgery II, Osaka University Medical School, Suita, Japan.
T
T
Tsujinaka
J
J
Fujita
C
C
Ebisui
M
M
Yano
E
E
Kominami
K
K
Suzuki
K
K
Tanaka
A
A
Katsume
Y
Y
Ohsugi
H
H
Shiozaki
M
M
Monden
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D001835:Body Weight; D002154:Calpain / Q000235:genetics; D002401:Cathepsin B / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000235:genetics; D010450:Endopeptidases; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009097:Multienzyme Complexes / Q000235:genetics; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D009133:Muscular Atrophy / Q000473:pathology / Q000517:prevention & control*; D009929:Organ Size; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018123:Receptors, Interleukin / Q000276:immunology*; D019947:Receptors, Interleukin-6; D014452:Ubiquitins / Q000235:genetics
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015850:Interleukin-6; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D014452:Ubiquitins; D002403:Cathepsins; D010450:Endopeptidases; D002154:Calpain; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C534280:Ctsl protein, rat; D046988:Proteasome Endopeptidase Complex