Depression of liver metabolism and induction of cytokine release by diphtheria and tetanus toxoids and pertussis vaccines: role of Bordetella pertussis cells in toxicity.
A 24-h pretreatment of mice with diphtheria and tetanus toxoids and whole-cell pertussis vaccines depressed liver cytochrome P-450 and therefore prolonged hexobarbital-induced sleeping time in mice. The depression of liver drug metabolism by a cellular vaccine containing a mutated pertussis toxin was less marked than that induced by the wild-type vaccines, indicating that the mutated vaccine might have lower toxicity in this regard. The wild-type vaccines decreased microsomal P-450 levels by 50%, while the mutated whole-cell vaccine had a less marked effect (a decrease of 30%), paralleling the results obtained in sleeping time experiments. Furthermore, an acellular mutated vaccine did not affect liver drug metabolism, indicating a role of the whole bacterial cell in this side effect. All the cellular vaccines studied induced high serum interleukin-6 levels; on the other hand, the acellular mutated vaccine induced very low interleukin-6 levels, indicating that the whole bacterial cell is also important for interleukin-6 induction. All vaccines studied were very poor tumor necrosis factor inducers.
Fantuzzi
G
G
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Sironi
M
M
Delgado
R
R
Cantoni
L
L
Rizzardini
M
M
Carelli
M
M
Marsili
I
I
Ghiara
P
P
Ghezzi
P
P
D000818:Animals; D001886:Bordetella pertussis / Q000472:pathogenicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004168:Diphtheria Toxoid / Q000276:immunology; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000276:immunology*; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D010567:Pertussis Vaccine / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D004168:Diphtheria Toxoid; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D015850:Interleukin-6; D010567:Pertussis Vaccine; D013745:Tetanus Toxoid; D014409:Tumor Necrosis Factor-alpha; D003577:Cytochrome P-450 Enzyme System