In-vivo treatment with 5-azacytidine causes degeneration of central lymphatic organs and induces autoimmune disease in the chicken.
In-vitro evidence suggests that DNA methylation may be involved in the development of forbidden immune responses that can result in autoimmune disease. In the present study we examined in-vivo effects of 5-azacytidine (5-azaC), a substance that inhibits DNA methylation, on the immune system and the occurrence of a spontaneous autoimmune disease in the chicken model. We found that (1) treatment of young normal chickens with 1.0 mg/kg 5-azaC on 7 consecutive days caused a rapid degeneration of the central lymphoid organs thymus and bursa; (2) this regimen with 5-azaC apparently inhibited B cell maturation, as the frequency of cytoplasmic Ig+ plasma cells in the bone marrow was found to be significantly reduced, whereas the total number of bone marrow cells was unchanged; and (3) a chronic low-dose (0.5 and 1.0 mg/kg) application of 5-azaC through 6 weeks was found to significantly enhance the spontaneous autoimmune thyroiditis in newly hatched chickens of the Cornell C strain, as determined by anti-thyroglobulin autoantibody titres and histological analysis of thyroid gland infiltration. The possible implications of these data for the generation of pathogenic autoimmune responses are discussed.
Schauenstein
K
K
Institute of General and Experimental Pathology, University of Innsbruck, Austria.
Csordas
A
A
Krömer
G
G
Dietrich
H
H
Wick
G
G
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000473:pathology; D001374:Azacitidine / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D002645:Chickens; D008206:Lymphatic Diseases / Q000139:chemically induced* / Q000473:pathology; D008221:Lymphoid Tissue / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity
D001374:Azacitidine