title: In vitro pyrogenicity of the diphtheria, tetanus and acellular pertussis components of a trivalent vaccine.
abstract: We have earlier found that a trivalent vaccine, containing antigenic components from both Gram-positive and Gram-negative bacteria, induced secretion of the endogenous pyrogen interleukin 6 (IL-6) when added to fresh human blood in vitro. The results of the present study showed that the IL-6 secretion was induced by toxoids derived from the Gram-positive bacterium Corynebacterium diphtheriae. However, fresh whole blood from different donors reacted differently to the stimulation. The blood from some donors induced secretion of large concentrations of IL-6, while the blood from other donors induced essentially no IL-6 secretion as a response to stimulation with diphtheria toxoid or a mixture of diphtheria and tetanus toxoids. Repeated testing over several years using blood from the same donor confirmed a donor-dependency of the reaction. This donor-dependency was only found for the toxoid, since blood from all donors reacted with approximately similar IL-6 production to stimulation by endotoxin from the Gram-negative bacterium Escherichia coli, known to be mediated via the toll-like receptor (TLR) 4. Also, no donor-dependecy was found to highly purified lipoteichoic acid from the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus, known to be mediated via TLR-2 and TLR-6. The receptors involved in stimulation by diphtheria toxoid are not known, but may differ from those used by endotoxin and lipoteichoic acid.
authors.affiliation: Medical Products Agency, P.O. Box 26, SE-75103 Uppsala, Sweden. gunnar.carlin@mpa.se
authors.forename: Gunnar
authors.initials: G
authors.lastname: Carlin
authors.forename: Eila
authors.initials: E
authors.lastname: Viitanen
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D001412:Bacillus subtilis / Q000276:immunology; D003353:Corynebacterium diphtheriae / Q000276:immunology; D004168:Diphtheria Toxoid / Q000737:chemistry; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000737:chemistry*; D004731:Endotoxins / Q000032:analysis* / Q000494:pharmacology; D004926:Escherichia coli; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood*; D008033:Limulus Test; D008070:Lipopolysaccharides / Q000494:pharmacology; D011749:Pyrogens / Q000032:analysis* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000276:immunology; D013682:Teichoic Acids / Q000494:pharmacology
chemical_list: D000907:Antibodies, Bacterial; D004168:Diphtheria Toxoid; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D004731:Endotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011749:Pyrogens; D013682:Teichoic Acids; C009900:lipoteichoic acid