Effect of gram-negative endotoxin on levels of serum corticosterone, TNF alpha, circulating blood cells, and the survival of rats.
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 E. 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 (greater than 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 doses which produced greater than 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 x 10(7) U/ml, much higher than the maximal TNF alpha levels produced by LPS, 1-2 x 10(5) 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.
Feuerstein
G
G
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
Hallenbeck
J M
JM
Vanatta
B
B
Rabinovici
R
R
Perera
P Y
PY
Vogel
S N
SN
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood*; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006400:Hematocrit; D007962:Leukocytes / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000097:blood* / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003345:Corticosterone