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 wh ole-cell pertussis vaccines depressed liver cytochrome P-450 and there fore prolonged hexobarbital-induced sleeping time in mice. The depress ion of liver drug metabolism by a cellular vaccine containing a mutate d pertussis toxin was less marked than that induced by the wild-type v accines, indicating that the mutated vaccine might have lower toxicity in this regard. The wild-type vaccines decreased microsomal P-450 lev els by 50%, while the mutated whole-cell vaccine had a less marked eff ect (a decrease of 30%), paralleling the results obtained in sleeping time experiments. Furthermore, an acellular mutated vaccine did not af fect liver drug metabolism, indicating a role of the whole bacterial c ell in this side effect. All the cellular vaccines studied induced hig h serum interleukin-6 level; on the other hand, the acellular mutated vaccine induced very low interleukin-6 levels, indicating that the who le bacterial cell is also important for interleukin-6 induction. All v accines studied were very poor tumor necrosis factor inducers.