Regulation of lipopolysaccharide-induced tumor necrosis factor production by cyclosporin A in mice primed with muramyl dipeptide.
The effect of cyclosporin A (CsA) on tumor necrosis factor (TNF) or interleukin-6 (IL-6) production was evaluated in vivo in primed or unprimed mice challenged with lipopolysaccharide (LPS). Both pretreatment with BCG infection or with muramyl dipeptide (MDP) prior to LPS challenge resulted in an increase in the cytokine bioactivity level in the blood. CsA administration inhibited the TNF production. In unprimed mice, either normal or sensitized to LPS lethality by galactosamine treatment, a marked decrease in the cytokine level was observed after injection of CsA. After adrenalectomy, the yield of both TNF and IL-6 following LPS injection was markedly elevated but decreased by CsA administration. Ex vivo experiments have shown that the inhibitory effect of CsA could be demonstrated at the level of macrophages from mice previously given the drug. If mice had received MDP, in vitro responses of cells to LPS were enhanced but again CsA decreased the mRNA expression and protein secretion.
Le Contel
C
C
Laboratory of Immunopharmacology, CNRS URA 1283, Paris, France.
Beigneux
A P
AP
Huang
J
J
Parant
M A
MA
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000315:Adrenalectomy; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D005688:Galactosamine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D014376:Tuberculosis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D001427:Bacterial Toxins; D004731:Endotoxins; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C027952:salmonella toxin; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D005688:Galactosamine; D016572:Cyclosporine