Effects of human interferon alphaofn and interferon gamma(IFNR) on xenografted human thyroid tissue in severe combined immunodeficient (SCID) and nude mice

The development of autoimmune thyroid disease has been reported during IFNH therapy for chronic hepatitis, but pathogenesis is still unclear. We have now studied in vivo effects of IFNi and IFN administration on human thyroid tissue xenografted into 2 different strains of mice (nude and SCID). Human lymphocytes are lysed in the nude, but survive in the SCID mice. Human thyroid tissue [Graves' dis. (GD)n=3, Hashimoto's (HT)n=3, normal thyroid tissue (N)n=-3] were xenografted into 33 SCID mice (0.8 g/mouse) pretreated with anti-asialo GM-I & radiation, and 15 nude mice. I wk. after xenografting, SCID and nude mice were divided into 3 groups: group A was treated with IFN tp (ZOOO u/mouse) 3 x wk; group B was treated with IFN ; group C was treated with PBS only (control). Blood was taken q. 2 wks for thyroid antibodies. After 6 wks, mice were sacrificed. Xenografted tissue was examined for thyrocyte HLA-DR and ICAM-I expression. SCID mice xenografted with GD and HT in groups A & B showed higher autoantibodies than in group C. SCID mice xenografted with N showed no thyroid antibodies in any group. Nude mice xenograted with GD or HT showed disappearing thyroid antibodies in all groups. Thyrocyte HLA-DR and ICAM-I expression were markedly increased in groups A & B in SCID mice xenografted with GD or HT.In contrast, HLA-DR and ICAM-I were no different between group A or C in nude mice xenografted with GD or HT. Thus, (I) IFN & IFN cause thyroid antibody production in GD and HT, but not in N in this SCID model;(2) IFN has indirect effects on thyrocytes probably through action on local T and B lymphocytes; (3) IFN* has a direct effect on thyrocytes.