Interleukin-6 and cachexia in ApcMin/+ mice.
The Apc(Min/+) mouse has a mutation in the Apc tumor suppressor gene and develops intestinal polyps, beginning at 4 wk of age. This mouse develops cachexia by 6 mo, characterized by significant loss of muscle and fat tissue. The purpose of the present study was to determine the role of circulating interleukin-6 (IL-6) and the polyp burden for the development of cachexia in Apc(Min/+) mice. At 26 wk of age, mice exhibiting severe cachectic symptoms had a 61% decrease in gastrocnemius muscle weight, complete loss of epididymal fat, a 10-fold increase in circulating IL-6 levels, and an 89% increase in intestinal polyps compared with mildly cachectic animals. Apc(Min/+)/IL-6(-/-) mice did not lose gastrocnemius muscle mass or epididymal fat pad mass while overall polyp number decreased by 32% compared with Apc(Min/+) mice. Plasmid-based IL-6 overexpression in Apc(Min/+)/IL-6(-/-) mice led to a decrease in gastrocnemius muscle mass and epididymal fat pad mass and increased intestinal polyp burden. IL-6 overexpression did not induce cachexia in non-tumor-bearing mice. These data demonstrate that IL-6 is necessary for the onset of adipose and skeletal muscle wasting in the Apc(Min/+) mouse and that circulating IL-6 can regulate Apc(Min/+) mouse tumor burden.
Baltgalvis
Kristen A
KA
Department of Exercise Science, University of South Carolina, Public Health Research Center, 921 Assembly Street, Columbia, SC 29208, USA.
Berger
Franklin G
FG
Pena
Maria Marjorette O
MM
Davis
J Mark
JM
Muga
Stephanie J
SJ
Carson
James A
JA
D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001835:Body Weight; D002100:Cachexia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018274:Electroporation; D015870:Gene Expression / Q000276:immunology; D017491:Genes, APC; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology; D010957:Plasmids; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012720:Severity of Illness Index
D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse