Modulation of benzo[a]pyrene induced immunotoxicity in mice actively immunized with a B[a]P-diphtheria toxoid conjugate.
Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also toxic for mammalian immune cells. To develop a prophylactic immune strategy against detrimental effects of B[a]P, we have immunized mice with a B[a]P-diphtheria toxoid conjugate vaccine. We showed that high levels of antibodies against B[a]P and its metabolites modulate the redistribution of these PAHs in the blood. After immunization, increased levels of B[a]P and its metabolites were recovered in the blood. B[a]P significantly suppressed the proliferative response of both T and B cells after a sub-acute administration, an effect that was completely reversed by vaccination. In immunized mice also the immunotoxic effect of B[a]P on IFN-gamma, IL-12, TNF-alpha production and the reduced B cell activation was restored. Finally, our results showed that specific antibodies inhibited the induction of Cyp1a1 by B[a]P in lymphocytes and Cyp1b1 in the liver, enzymes that are known to convert the procarcinogen B[a]P to the ultimate DNA-adduct forming metabolite, a major risk factor of chemical carcinogenesis. Thus, we demonstrate that vaccination with a B[a]P conjugate vaccine based on a carrier protein used in licensed human vaccines reduces immunotoxicity and possibly other detrimental effects associated with B[a]P.
Schellenberger
Mario T
MT
Institute of Immunology, LNS/CRP-Santé, Luxembourg, Grand Duchy of Luxembourg.
Grova
Nathalie
N
Willième
Stéphanie
S
Farinelle
Sophie
S
Prodhomme
Emmanuel J F
EJ
Muller
Claude P
CP
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000502:physiology; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D002478:Cells, Cultured; D004165:Diphtheria / Q000276:immunology / Q000517:prevention & control; D004168:Diphtheria Toxoid / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D005260:Female; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination / Q000379:methods*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use
D000906:Antibodies; D004168:Diphtheria Toxoid; D006241:Haptens; D018074:Vaccines, Conjugate; D001564:Benzo(a)pyrene