AJP - Endocrinology and Metabolism, Vol 256, Issue 6 E725-E731, Copyright © 1989 by American Physiological Society
Reversal of the toxic effects of cachectin by concurrent insulin administration
D. L. Fraker, M. J. Merino and J. A. Norton
Surgical Metabolism Section, National Cancer Institute, Bethesda, Maryland 20892.
Rats treated with recombinant human tumor necrosis factor-cachectin, 100
micrograms/kg ip twice daily for 5 consecutive days, had a 56% decrease in
food intake, a 54% decrease in nitrogen balance, and a 23-g decrease in
body weight gain vs. saline-treated controls. Concurrent neutral protamine
hagedorn insulin administration of 2 U/100 g sc twice daily reversed all of
these changes to control levels without causing any treatment deaths. The
improvement seen with insulin was dose independent. Five days of cachectin
treatment caused a severe interstitial pneumonitis, periportal inflammation
in the liver, and an increase in wet organ weight in the heart, lungs,
kidney, and spleen. Concurrent insulin treatment led to near total reversal
of these histopathologic changes. Cachectin treatment did not significantly
change blood glucose levels from control values of 130-140 mg/dl, but
insulin plus cachectin caused a significant decrease in blood glucose from
1 through 12 h after injection. Administration of high-dose insulin can
near totally reverse the nutritional and histopathologic toxicity of
sublethal doses of cachectin in rats.
