title: In vivo administration of IL-1 induces thymic hypoplasia and increased levels of serum corticosterone.
abstract: Administration of IL-1 alpha or IL-1 beta to normal mice induces a decrease in thymic cellularity, the magnitude of which depends on the number of injections and dose of IL-1. Twice daily injections of 200 ng of IL-1 alpha or -beta for 4 days results in a 90% decrease in thymic cellularity, which regenerated after cessation of treatment. Study of thymocyte subpopulations revealed that the number of CD4+/CD8+ thymocytes was dramatically decreased in IL-1-treated mice. Functional assessment of the CD4-/CD8- population from treated animals showed that these cells had adequate mitogenic responses in vitro and that the proportion of these cells in cycle was not different from control CD4-/CD8- cells. IL-1 treatment also prevented the regeneration of thymic cellularity after irradiation. The use of strains of mice differing genetically at the Ly 1 locus to construct radiation bone marrow chimeras demonstrated that bone marrow-derived thymocyte precursors were able to seed the thymus in the IL-1-treated animals. Again, however, the CD4+/CD8+ thymocyte population was significantly decreased. Thymic repopulation occurred upon cessation of IL-1 therapy. Finally, we determined that a single i.p. injection of IL-1 caused a three-fold increase in serum corticosterone levels, which peaked approximately 3 h after IL-1 administration. Thus, an IL-1-dependent increase in serum corticosterone levels may be responsible for the observed thymic hypoplasia.
authors.affiliation: Immunex Corporation, Seattle, WA 98101.
authors.forename: P J
authors.initials: PJ
authors.lastname: Morrissey
authors.forename: K
authors.initials: K
authors.lastname: Charrier
authors.forename: A
authors.initials: A
authors.lastname: Alpert
authors.forename: L
authors.initials: L
authors.lastname: Bressler
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood*; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000008:administration & dosage*; D008206:Lymphatic Diseases / Q000097:blood / Q000209:etiology* / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011828:Radiation Chimera; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology*
chemical_list: D007375:Interleukin-1; D003345:Corticosterone