EFFECT OF GRAM-NEGATIVE ENDOTOXIN ON LEVELS OF SERUM CORTICOSTERONE, TNF-ALPHA, CIRCULATING BLOOD-CELLS, AND THE SURVIVAL OF RATS

  • 1 March 1990
    • journal article
    • research article
    • Vol. 30  (3) , 265-278
Abstract
The relationship between serum tumor necrosis factor (TNF.alpha.), circulating blood cells, plasma corticosterone (CS), and survival was studied in conscious rats injected intravenously with Escherichia coli lipopolysaccharide (LPS, 0.0001-28.8 mg/kg). The TNF.alpha. response was dose-related, peaked at 90-120 min after LPS injection, and subsided 6 hr later. The CS response showed an earlier onset, prolonged (> 12 hr) duration, and a broader dose-response pattern. White blood cells (WBC) and platelet depletion peaked at 2-4 and 24-48 hr post-LPS, respectively; however, no changes in the cell count were observed at LPS dose which produced > 50% maximal increase in TNF.alpha. levels. Survival curves for each of the LPS doses were significantly different from the doses of LPS which elicited TNF.alpha. release. Systemic injection of human recombinant TNF.alpha. (h-rTNF.alpha.), which produced plasma levels of TNF.alpha. 10 .times. 107 U/ml, much higher than the maximal TNF.alpha. levels produced by LPS, 1-2 .times. 105 U/ml, failed to affect survival, plasma WBC, or hematocrit. Our data suggest that factors other than TNF.alpha. produced by high doses of LPS are essential in eliciting LPS-induced death.