Yamaura Katsunori, Ogawa Kohei, Yonekawa Taeko, Nakamura Tomonori, Yano Shingo, Ueno Koichi
Department of Molecular Pharmacology and Pharmacotherapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, Japan.
Biol Pharm Bull. 2002 Feb;25(2):201-5. doi: 10.1248/bpb.25.201.
The causal relationship between the inhibition of antibody production and liver injury induced by single doses of acetaminophen (APAP) was investigated in mice. The liver injury and antibody production were evaluated using the serum transaminase activity and the number of antibody forming cells against sheep red blood cells (SRBC), respectively. The relevance of APAP hepatotoxicity with inhibiting antibody production was elucidated in fasted and fed mice treated with a single oral administration of APAP. In fasted mice, the oral administration of APAP produced serious liver injury, while it was not the case in the fed mice. As the antibody production was measured under these conditions, APAP significantly depressed the antibody production in fed mice as well as in fasted mice. The rate of B220 positive cells in the splenocytes was significantly decreased by APAP administration in both the fasted and fed mice. Splenocytes proliferative responses following mitogenic stimulation with concanavalin A or lipopolysaccharide were inhibited by APAP. Moreover, APAP added directly to the splenocyte culture also inhibited the in vitro antibody-producing response to SRBC. These findings indicate that the APAP-induced depression of antibody production may not be a secondary response to APAP-hepatitis, but may be a primary response to APAP.
在小鼠中研究了单剂量对乙酰氨基酚（APAP）诱导的抗体产生抑制与肝损伤之间的因果关系。分别使用血清转氨酶活性和针对绵羊红细胞（SRBC）的抗体形成细胞数量来评估肝损伤和抗体产生。在单次口服给予APAP的禁食和喂食小鼠中阐明了APAP肝毒性与抑制抗体产生的相关性。在禁食小鼠中，口服APAP会产生严重的肝损伤，而在喂食小鼠中则不然。在这些条件下测量抗体产生时，APAP显著抑制了喂食小鼠和禁食小鼠中的抗体产生。在禁食和喂食小鼠中，给予APAP均显著降低了脾细胞中B220阳性细胞的比例。用刀豆球蛋白A或脂多糖进行有丝分裂原刺激后，脾细胞的增殖反应受到APAP的抑制。此外，直接添加到脾细胞培养物中的APAP也抑制了对SRBC的体外抗体产生反应。这些发现表明，APAP诱导的抗体产生抑制可能不是对APAP肝炎的继发反应，而是对APAP的原发反应。
