Aschkenasy A
Ann Nutr Aliment. 1975;29(2):137-50.
One hundred eleven male adult rats of a pathogen-free Sherman or Charles River strain were divided into 3 series. Each of them contained non-treated controls and rats treated with intraperitoneal (i.p.) injections of DL-ethionine (E) [75 mg/d p. 100 g] for 6 weeks (series 1) or for only 2 weeks (series 2 and 3). Series 1 and 2 included also rats injected simultaneously with E and DL-methionine (68.4 mg/d p. 100 g). In the series 2 there were also groups receiving at the same time E, ME and tryptophan (5 mg/d p. 100 g) or E, Me and ATP (1.65 mg/d), and in the series 3, groups were injected with E + adenosine (31.2 mg/d p. 100 g) and (or) uridine (284 mg/d p. 100 g). All animals were immunized i.p. 1 week before killing with sheep red blood cells (SRBC): either 2.4 X 10(9) SRBC p. 100 g without adjuvant (series 1 and 2) or 1 X 10(9) SRBC with Freund's adjuvant added (series 3). Rosette-and plaque-forming cells (RFC and PFC) were counted in the spleen, and titers of serum hemagglutinins and hemolysins were determined with separation of 2-mercaptoethanol-resistant IgG from non-resistant immunoglobulins. E provoked within 2 weeks a drastic inhibition of the immune responses: drop in the RFC and PFC levels p. 10(6) (approximately 2900 leads to approximately 320 and approximately 415 leads to 40 respectively, in the study 3), and significant decrease in the serum antibody titer, especially IgG. Addition of Me still amplified the immunosuppression. Supplementation with tryptophan, ATP, adenosine and (or) uridine was also ineffective. Though not displaying any immunoprotective potency, Me partly neutralized the non-immunological effects of E: arrest of the body growth and involution of lymphoid organs and male genital organs, particularly apparent after 6 weeks of treatment. In conclusion, the ethionine-induced immunosuppression does not result from a metabolic exclusion of labile methyl groups or from an acute ATP deficiency due to an excess trapping of adenine as S-adenosyl-ethionine. Lack of pyrimidines or tryptophan must also be discarded. On the other hand, the possibility of maintaining the immunosuppressive activity of E, while reducing the toxicity of this compound, by addition of Me deserves to be emphasized.
将111只无特定病原体的谢尔曼或查尔斯河品系成年雄性大鼠分为3组。每组都包含未处理的对照组以及腹腔注射DL-乙硫氨酸（E）[75mg/（d·100g体重）]6周（第1组）或仅2周（第2组和第3组）的大鼠。第1组和第2组还包括同时注射E和DL-甲硫氨酸（68.4mg/（d·100g体重））的大鼠。在第2组中，还有同时接受E、甲硫氨酸和色氨酸（5mg/（d·100g体重））或E、甲硫氨酸和ATP（1.65mg/d）的组，在第3组中，有注射E+腺苷（31.2mg/（d·100g体重））和（或）尿苷（284mg/（d·100g体重））的组。所有动物在处死前1周腹腔注射绵羊红细胞（SRBC）进行免疫：第1组和第2组为2.4×10⁹个SRBC/100g体重且无佐剂，第3组为1×10⁹个SRBC并添加弗氏佐剂。计数脾脏中的玫瑰花结形成细胞和空斑形成细胞（RFC和PFC），并通过从非抗性免疫球蛋白中分离2-巯基乙醇抗性IgG来测定血清血凝素和溶血素的效价。E在2周内引发了免疫反应的剧烈抑制：RFC和PFC水平下降（第3组中，每10⁶个细胞分别从约2900降至约320和约415降至40），血清抗体效价显著降低，尤其是IgG。添加甲硫氨酸仍会增强免疫抑制作用。补充色氨酸、ATP、腺苷和（或）尿苷也无效。虽然甲硫氨酸没有显示出任何免疫保护作用，但它部分抵消了E的非免疫作用：身体生长停滞以及淋巴器官和雄性生殖器官萎缩，在治疗6周后尤为明显。总之，乙硫氨酸诱导的免疫抑制并非由于不稳定甲基的代谢排除或由于腺嘌呤作为S-腺苷乙硫氨酸的过度捕获导致的急性ATP缺乏。嘧啶或色氨酸的缺乏也必须排除。另一方面，值得强调的是，通过添加甲硫氨酸在降低该化合物毒性的同时维持E的免疫抑制活性的可能性。
