Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation.
Cachexia is a potentially lethal syndrome of unknown etiology characterized by anorexia, weight loss, and protein wasting that frequently complicates the treatment of chronic inflammation and cancer. Cachectin/TNF was isolated during the search for a humoral mediator of cachexia and found to stimulate the breakdown of energy stores from adipocytes and myocytes in vitro, but the chronic effects of the monokine in vivo are not known. Sublethal doses of recombinant human cachectin administered twice daily for 7-10 d caused cachexia in rats, as evidenced by reduced food intake, weight loss, and depletion of whole-body lipid and protein stores. Significant anemia is also observed and found to be the result of decreased red blood cell mass, not expanded plasma volume. Leukocytosis and histopathological evidence of tissue injury and inflammation are observed in several organs, including omentum, liver, spleen, and heart. These data suggests that the exposure of the normal host to cachectin is capable of inducing a pathophysiological syndrome of cachexia, anemia, and inflammation similar to that observed during inflammatory states or malignancy.
Tracey
K J
KJ
Laboratory of Surgical Metabolism, New York Hospital-Cornell University Medical Center, New York, New York 10021.
Wei
H
H
Manogue
K R
KR
Fong
Y
Y
Hesse
D G
DG
Nguyen
H T
HT
Kuo
G C
GC
Beutler
B
B
Cotran
R S
RS
Cerami
A
A
D000740:Anemia / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000139:chemically induced* / Q000473:pathology; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D007249:Inflammation / Q000139:chemically induced; D007964:Leukocytosis / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha