Acetaminophen-induced immunosuppression associated with hepatotoxicity in mice.
We investigated the influence of acetaminophen (APAP), an analgesic and hepatotoxic agent, on the immune system in mice. The activity of serum glutamic-pyruvic transaminase was markedly increased by about 200 fold compared to that of the vehicle control following intraperitoneal injection of 400 mg/kg of APAP. In vivo antibody-producing responses to SRBC was significantly inhibited by APAP in a dose-dependent manner, while in vivo T cell-independent antibody-producing responses to TNP-Ficoll was not inhibited. The addition of thymocytes from APAP-treated mice suppressed the response to SRBC in vitro. Thymocyte blastogenesis following mitogenic stimulation with concanavalin A was also inhibited by injection of APAP. The delayed-type hypersensitivity response and mixed lymphocyte reaction, which are used to evaluate cell-mediated immunity, were also significantly reduced after treatment with APAP. These results indicate that APAP suppresses the humoral and cell-mediated immune responses at a dose that causes liver injury.
Ueno
K
K
Laboratory of Molecular Pharmacology and Pharmacotherapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, Japan. kueno@p.chiba-u.ac.jp
Yamaura
K
K
Nakamura
T
T
Satoh
T
T
Yano
S
S
D000082:Acetaminophen / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000473:pathology; D007108:Immune Tolerance / Q000187:drug effects*; D007111:Immunity, Cellular / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology
D008934:Mitogens; D000082:Acetaminophen; D000410:Alanine Transaminase