SEPSIS STIMULATES POLYAMINE BIOSYNTHESIS IN THE LIVER AND INCREASES TISSUE-LEVELS OF ORNITHINE DECARBOXYLASE MESSENGER-RNA

The influence of sepsis on polyamine metabolism in the liver was studi ed in rats. Sepsis was induced by cecal ligation and puncture; control rats were sham-operated. Sepsis resulted in increased concentrations in liver tissue of putrescine and spermidine and stimulated activity o f the enzymes ornithine decarboxylase (ODC) and s-adenosylmethionine d ecarboxylase. A similar metabolic response was seen following the subc utaneous injection of 1 mg/kg of endotoxin or following the intraperit oneal injection of 100 mu g/kg of human recombinant tumor necrosis fac tor (TNF)-alpha or interleukin-1 alpha (IL-1 alpha). ODC mRNA levels d etermined by Northern blots were increased in liver tissue of septic r ats, suggesting that the increase in ODC activity may be regulated at the transcriptional level although increased stability of the messenge r could give rise to similar results. Treatment of rats with either TN F antiserum, recombinant IL-1 receptor antagonist, or the glucocortico id receptor antagonist RU 38486, did not prevent the sepsis-induced in crease in hepatic ODC activity. The data suggest that sepsis stimulate s the biosynthesis of polyamines in liver tissue and that this respons e to sepsis may not primarily be mediated by TNF, IL-1, or glucocortic oids. The biological role of increased liver polyamines during sepsis, in particular their relationship with the synthesis of acute phase pr oteins, remains to be determined.