THE EFFECT OF A BOLUS INJECTION OF TNF-ALPHA AND IL-1-BETA ON HEPATICENERGY-METABOLISM IN RATS

The effects of intravenous bolus injection of tumor necrosis factor-al pha (TNF-alpha) and interleukin-1beta (IL-1 beta) on hepatic mitochond rial energy metabolism were investigated in rats. The rats were inject ed with 15 mu g/kg body wt of human recombinant TNF-alpha and IL-1 bet a. The hepatic energy charge decreased to 0.794 +/- 0.005 and 0.789 +/ - 0.006 in comparison with the sham control value of 0.838 +/- 0.007 a nd 0.835 +/- 0.011 at 12 and 24 hr after the treatment. The mitochondr ial redox state (NAD(+)/NADH) increased from 17.4 +/- 1.9, 16.6 +/- 1. 4, and 19.2 +/- 2.1 to 33.5 +/- 3.5, 27.8 +/- 2.8, and 30.9 +/- 2.6 co ncomitant with an increase in arterial blood ketone body ratio (acetoa cetate/beta-hydroxybutyrate) from 0.49 +/- 0.04, 0.34 +/- 0.04, and 0. 44 +/- 0.09 to 1.00 +/- 0.16, 0.69 +/- 0.13, and 0.86 +/- 0.15 at 3, 1 2, and 24 hr after the treatment. Total ketone body concentration in l iver tissue and arterial blood was significantly lower at 24 hr after the treatment. State 3 respiration rate of isolated mitochondria incre ased by 29.2, 30.3, and 19.2% concomitant with an increase in oxidativ e phosphorylation rate by 26, 33.7, and 24.3% at 3, 12, and 24 hr afte r the treatment. These results showed that the administration of TNF-a lpha and IL-1 beta in rats induced a hypermetabolic state in hepatic m itochondrial energy metabolism, which is a pattern similar to sepsis a nd presumably a compensatory reaction to the increased energy consumpt ion. (C) 1995 Academic Press, Inc.