title: Spleen-specific development of germinal centers in rats treated with antithyroid drugs.
abstract: The antithyroid drugs (ATDs) methimazole (MMI) and propylthiouracil (PTU) have been used for treatment of hyperthyroidism for more than several decades, despite the fact that they are associated with adverse drug reactions that are thought to be autoimmune mediated. We therefore examined histopathologic responses in the immune system in male and female rats given MMI (2, 20 and 200 mg/kg/day, p.o., in experiment 1; 200 mg/kg/day, p.o., in experiment 3) or PTU (25 and 250 mg/kg/day, p.o., in experiment 2; 200 mg/kg/day, p.o., in experiment 3) for two weeks. In experiments 1 and 2, highest doses of MMI and PTU induced histopathologic changes in the spleen consistent with those in experiment 3 without any changes in the other peripheral lymphoid organs and tissues. In experiment 3, histopathological evaluation of the spleen along with hematological and bone marrow examinations were performed. In both male and female rats, MMI or PTU induced histopathological changes in the spleen characterized by development of germinal centers and an increase in the number of IgG-positive plasma cells in the red pulp; these changes were most prevalent in the MMI-treated female rats. Total red and white blood cell counts were decreased in the MMI-treated male and female rats; lymphocytes and monocytes were lower in male and female rats, respectively. Bone marrow nucleated cells were significantly lower in the MMI-treated males. This is the first study to demonstrate that ATDs induce spleen specific B-cell reactions in rats.
authors: Safety Research Department, ASKA Pharmaceutical Co., Ltd., 5-36-1 Shimosakunobe, Takatsu-ku, Kawasaki, Kanagawa213-8522, Japan.
authors: Motoko
authors: M
authors: Fukui
authors: Safety Research Department, ASKA Pharmaceutical Co., Ltd., 5-36-1 Shimosakunobe, Takatsu-ku, Kawasaki, Kanagawa213-8522, Japan.
authors: Norio
authors: N
authors: Fukui
authors: Product Research Department, ASKA Pharmaceutical Co., Ltd., 3-4-3 Sakaecho, Hamura, Tokyo 205-8501, Japan.
authors: Kuniyoshi
authors: K
authors: Sakai
authors: Product Research Department, ASKA Pharmaceutical Co., Ltd., 3-4-3 Sakaecho, Hamura, Tokyo 205-8501, Japan.
authors: Yuko
authors: Y
authors: Hasegawa
authors: Drug Discovery Department, ASKA Pharmaceutical Co., Ltd., 5-36-1 Shimosakunobe, Takatsu-ku, Kawasaki, Kanagawa213-8522, Japan.
authors: Shuji
authors: S
authors: Nagasaki
authors: Safety Research Department, ASKA Pharmaceutical Co., Ltd., 5-36-1 Shimosakunobe, Takatsu-ku, Kawasaki, Kanagawa213-8522, Japan.
authors: Seiji
authors: S
authors: Shibata
authors: Safety Research Department, ASKA Pharmaceutical Co., Ltd., 5-36-1 Shimosakunobe, Takatsu-ku, Kawasaki, Kanagawa213-8522, Japan.
authors: Sei-Ichi
authors: S
authors: Araki
authors: Safety Research Department, ASKA Pharmaceutical Co., Ltd., 5-36-1 Shimosakunobe, Takatsu-ku, Kawasaki, Kanagawa213-8522, Japan.
authors: Mitsui
authors: M
authors: Isobe
authors: Developmental Research Center, ASKA Pharmaceutical Co., Ltd., 5-36-1 Shimosakunobe, Takatsu-ku, Kawasaki, Kanagawa213-8522, Japan.
authors: Shigeru
authors: S
authors: Hisada
keywords: antithyroid drug; autoantibody; germinal center; methimazole; propylthiouracil; spleen