[Immunosuppressive effect of ethionine in rats. Resistance of this effect to methionine, tryptophan, ATP, adenosine and uridine].
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.
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D005001:Ethionine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005856:Germ-Free Life; D007109:Immunity / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D008715:Methionine / Q000494:pharmacology*; D009929:Organ Size; D051381:Rats; D012263:Ribonucleosides / Q000494:pharmacology*; D014364:Tryptophan / Q000494:pharmacology*; D014529:Uridine / Q000494:pharmacology
D007166:Immunosuppressive Agents; D012263:Ribonucleosides; D014364:Tryptophan; D000255:Adenosine Triphosphate; D008715:Methionine; D000241:Adenosine; D014529:Uridine; D005001:Ethionine
Effet immunodépresseur de l'éthionine chez le rat. Résistance de cet effet a l'administration de méthionine, de tryptophane, d'ATP, d'adénosine et d'uridine