Depletion of lymphoid tissues by tilorone. Ultrastructure and synergistic interaction with antilymphocyte serum.
Antilymphocyte serum (ALS) caused lymphocyte depletion and shrinkage of thymus-dependent areas in spleen and lymph nodes of rats. Tilorone also depleted T lymphocytes, but light- and electron-microscopic examination revealed hyperplasia and vacuolation of the interdigitating cells that remained in the thymus-dependent areas, rather than shrinkage. These changes were not mediated by the adrenal gland. The combination of agents had a synergistic effect on the thymus-dependent areas in the spleen, lymph nodes, Peyer's patches, and bronchial-associated lymphoid tissue, all of which were severely depleted but maintained their normal dimensions. The combination of ALS and a tilorone analog that was capable of depleting lymph node but not spleen, gave a synergistic effect only in lymph node and not in spleen. Tilorone effects were transient, whereas ALS produced a long-lasting depletion. Administration of the two drugs at different times were synergistic only during the brief period of tilorone's effectiveness. The synergistic effects on T lymphocytes correlated well with immunosuppressive potency of the combined drugs on a T-lymphocyte-mediated auto-immune disease.
D000818:Animals; D000961:Antilymphocyte Serum / Q000494:pharmacology*; D003907:Dexamethasone / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D005449:Fluorenes / Q000494:pharmacology*; D008198:Lymph Nodes / Q000187:drug effects / Q000648:ultrastructure; D008221:Lymphoid Tissue / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000187:drug effects / Q000648:ultrastructure; D013601:T-Lymphocytes / Q000187:drug effects; D013994:Tilorone / Q000494:pharmacology*; D013997:Time Factors
D000961:Antilymphocyte Serum; D005449:Fluorenes; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone; D013994:Tilorone