A preliminary report of circadian effects of interleukin-2 (IL-2) on the activity of enzymes of intermediary metabolism of mice.
Since it previously has been reported that IL-2 has profound circadian dependent effects upon DNA synthesis in the liver of mice (Scheving et al., 1988; Tsai et al., 1988) the effects of IL-2 on enzyme activities were studied. The objective was to determine the effect of IL-2 when administered at different times to mice who were fed ad libitum, and standardized to 12 h of light alternating with 12 h of dark. Three groups were injected intraperitoneally with either 1 or 4 mg/kg of IL-2, one group was given the vehicle only. The treatment time for each dose and the vehicle was a 2 h into the light for one group and the other was at 2 h into the dark span. Subgroups of 5 mice were killed 4, 8, 12, 16, 20, 24, and 30 h after each treatment, livers were taken and frozen to await preparation and analysis of enzyme activities by our standard procedures. When treatment was in the light span IL-2 had no statistically significant effect on enzymes of lipid, carbohydrate or amino acid metabolism. On the contrary when treatment was given in the dark span IL-2 produced statistically significant increases in enzymes of glycolysis, and lipid synthesis beginning 8 h after treatment (changes ranged from 20 to 43%) with both the higher and lower doses (higher doses always yielded higher activities), and these activities continued to increase through the 24 h post-treatment span (changes ranged from 42 to 64%). At 30 h, activities were returning to normal levels. Amino acid metabolism, on the other hand, was decreased during these post-treatment times (the range of decrease was from 18 to 44%). Thus, we report for the first time that the duration of time, pathway affected, as well as the magnitude of the effect seen and the dosage of IL-2 were all circadian-stage dependent even with two time point samplings. We believe, however, that these two time points represent different critical extremes in liver metabolism, but studies with denser sampling are planned. Interleukin-2 was generously supplied by Cetus Corp. of Emeryville, CA.
Feuers
R J
RJ
Div. Genetic Toxicology, National Center for Toxicological Research, Jefferson, AR.
Scheving
L A
LA
Tsai
T H
TH
Young
J D
JD
Scheving
L E
LE
D000410:Alanine Transaminase / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002940:Circadian Rhythm; D004798:Enzymes / Q000378:metabolism*; D005991:Glycerol Kinase / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D007376:Interleukin-2 / Q000494:pharmacology*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D011770:Pyruvate Kinase / Q000378:metabolism
D000596:Amino Acids; D004798:Enzymes; D007376:Interleukin-2; D000410:Alanine Transaminase; D005991:Glycerol Kinase; D011770:Pyruvate Kinase