title: Circumvention of the induction of resistance in murine experimental autoimmune thyroiditis by recombinant IL-1 beta.
abstract: Murine experimental autoimmune thyroiditis (EAT) is induced in genetically susceptible mice by immunization with mouse thyroglobulin (MTg). We have previously shown that raising the level of circulatory MTg for greater than or equal to 2 to 3 days, by the i.v. injection of soluble MTg or the infusion of thyroid-stimulating hormone, rendered these mice resistant to subsequent EAT induction. The Ag-specific resistance was mediated by CD4+ Ts cells, and the induction of unresponsiveness could be interfered with by injecting the T cell adjuvant poly(A).poly(U) 3 h after MTg pretreatment. To dissect further the cytokine signals involved in circumventing the induction of resistance, the effect of human rIL-1 beta was examined. As with poly(A).poly(U), mice given 4000 or 10,000 U or rIL-1 beta 3 h after deaggregated MTg (dMTg) were not resistant to EAT induced with MTg and adjuvant. Moreover, mice given 90,000 U or rIL-1 beta after dMTg and then immunized displayed very severe thyroiditis, strong in vitro proliferative response, and high antibody titers, compared with immunized controls, indicating a dose-dependent effect of rIL-1 beta. The intermediate dose of 10,000 U or rIL-1 beta was selected to determine the importance of time interval between dMTg and rIL-1 beta administration. Interference with the induction of suppression was more efficacious when rIL-1 beta was given at 3 h than at 24 h, but at 24 h it was no more effective than 4000 U given at this interval. In contrast, mice given 10,000 U of rIL-1 beta 3 h before dMTg and then challenged developed MTg antibodies but little thyroiditis, demonstrating that the interference with suppression of autoantibody responses can occur without altering the induction of suppression of thyroiditis. The injection of rIL-1 beta also led to a sharp but transient rise in serum IL-6. The short t1/2 of IL-6 suggests that any role played by IL-6 would require critical timing. Murine rIL-2 given at 1 and 2 days after dMTg had a minimal effect on induced resistance. Lastly, immunization of dMTg-pretreated mice with MTg and rIL-1 beta did not induce EAT, demonstrating that rIL-1 beta could not interfere with established suppression. Thus, the intervention by rIL-1 beta in MTg-induced suppression occurs at a critical time, early after the injection of dMTg but before the establishment of resistance.
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201.
authors.forename: G H
authors.initials: GH
authors.lastname: Nabozny
authors.forename: Y C
authors.initials: YC
authors.lastname: Kong
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D004334:Drug Administration Schedule; D007108:Immune Tolerance / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D008808:Mice, Inbred CBA; D011994:Recombinant Proteins; D013954:Thyroglobulin / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
chemical_list: D001324:Autoantigens; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011994:Recombinant Proteins; D013954:Thyroglobulin