Influence of tetanus and typhoid vaccines on hepatic drug metabolism.
Several experiments suggested that vaccines might inhibit liver drug-metabolizing enzymes, an assumption in agreement with other findings obtained with most immuno-enhancing agents. A direct, non-specific activation of macrophages with subsequent release of interleukin 1 may account for this inhibition. The purpose of the present study was to investigate whether tetanus and typhoid vaccines exerted such an influence on pentobarbital sleeping time in mice and antipyrine elimination in rabbits, both in vivo correlates of the activity of these enzymes. It is shown that tetanus (unlike typhoid) vaccination in both species can lead to a marked but transient impairment of hepatic drug metabolism in these conditions. The reason for this discrepancy is unclear. The assumption that aluminium hydroxide might play a critical role, as this adjuvant is included in the formulation of tetanus vaccine in contrast to that of typhoid vaccine, is not supported by our findings since aluminium hydroxide alone failed to exert any influence in our experimental conditions. Further studies are therefore warranted to elucidate the mechanism of this inhibition of the activity of hepatic drug-metabolizing enzymes.
Descotes
J
J
Department of Pharmacology, INSERM U-80/CNRS UA-1177/UCBL, Alexis Carrel Faculty of Medicine, Lyon, France.
Guillermin
A
A
Evreux
J C
JC
D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D001463:Barbiturates / Q000494:pharmacology; D005260:Female; D006207:Half-Life; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects; D013745:Tetanus Toxoid / Q000494:pharmacology*; D013997:Time Factors; D014436:Typhoid-Paratyphoid Vaccines / Q000494:pharmacology*
D001463:Barbiturates; D004364:Pharmaceutical Preparations; D013745:Tetanus Toxoid; D014436:Typhoid-Paratyphoid Vaccines; D000536:Aluminum Hydroxide; D000983:Antipyrine