Influence of endogenous glucocorticoid on endotoxin-induced production of circulating TNF-alpha.
Mice are quite resistant to LPS toxicity but even a small dose induced a monophasic production of circulating TNF. In BCG-treated mice challenged with LPS, the greater susceptibility was associated with the capacity of producing elevated levels of TNF in the blood. During pregnancy, after adrenalectomy, and particularly after treatment with galactosamine, smaller amounts of LPS were lethal in mice. Using adrenalectomized mice, which are less sensitive to LPS toxicity than galactosamine-treated mice, it was shown that smaller doses of LPS were effective in inducing TNF release in comparison with intact animals, and that larger concentrations of serum TNF were obtained. Pretreatment of adrenalectomized mice with MDP before LPS elicited a priming effect for an enhanced TNF production that reached levels comparable to that found in BCG-primed mice. Whatever was the yield of circulating TNF, the pattern of response was similar peaking at 1.5 to 2 h to LPS injection and returning to baseline values within 4 h. Prior administration of glucocorticoid was effective in preventing the release of serum TNF in adrenalectomized mice. The level and the kinetics of serum TNF following LPS injection were not modified in pregnant or in galactosamine-treated mice, and as in control animals glucocorticoid administration prior to LPS inhibited the TNF response.
Laboratory of Immunopharmacology, CNRS UPR 405, University Paris 6, France.
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D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage; D000315:Adrenalectomy; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005688:Galactosamine / Q000008:administration & dosage; D005938:Glucocorticoids / Q000502:physiology*; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D011247:Pregnancy; D011994:Recombinant Proteins / Q000633:toxicity; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000633:toxicity
D004731:Endotoxins; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D005688:Galactosamine