title: Picogram concentrations of endotoxin stimulate synthesis of IL-1 beta and TNF alpha by human peripheral blood mononuclear cells exposed to recombinant human C5a.
abstract: Endotoxemia, complement activation, and the generation of C5a occur in the course of sepsis, trauma, and the adult respiratory distress syndrome, clinical situations in which TNF and IL-1 are thought to play an important role. In the present studies, we examined the effect of picogram concentrations of endotoxin (LPS) on the synthesis of IL-1 beta and TNF alpha by human PBMC exposed to recombinant human C5a (rhuC5a). rhuC5a induced the synthesis of IL-1 beta by PBMC made in response to otherwise substimulatory levels of LPS. In the presence of rhuC5a, LPS concentrations from 10 pg to 1000 pg/ml substantially amplified IL-1 beta synthesis by PBMC compared to LPS alone. Since rhuC5a can induce transcription of IL-1 beta with minimal translation to cytokine protein, these studies support the concept that fM concentrations of LPS can combine with rhuC5a to provide the "second signal" for optimal translation of IL-1 beta mRNA.
authors.affiliation: Department of Medicine, New England Medical Center, Boston, MA 02111.
authors.forename: M
authors.initials: M
authors.lastname: Morin
authors.forename: R
authors.initials: R
authors.lastname: Schindler
authors.forename: G
authors.initials: G
authors.lastname: Wakabayashi
authors.forename: G
authors.initials: G
authors.lastname: Daumy
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: J A
authors.initials: JA
authors.lastname: Gelfand
mesh_terms: D015936:Complement C5a / Q000008:administration & dosage; D004306:Dose-Response Relationship, Immunologic; D004731:Endotoxins / Q000008:administration & dosage*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D004731:Endotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015936:Complement C5a