title: Adenovirus-mediated gene delivery of interleukin-10, but not transforming growth factor beta, ameliorates the induction of Graves' hyperthyroidism in BALB/c mice.
abstract: Interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) are well known anti-inflammatory cytokines. We have studied the effect of adenovirus-mediated IL-10 and TGF-beta gene delivery on the induction of Graves' hyperthyroidism in our mouse model that involves repeated injections of adenovirus expressing the thyrotropin receptor A subunit (AdTSHR). We first constructed adenoviruses encoding the two cytokines (AdIL10 and AdTGF(beta)) and confirmed expression by in vitro infection of COS cells. Susceptible BALB/c mice were injected twice with AdTSHR alone or together with AdIL10 or AdTGF(beta), and bled two weeks after the second immunization. Significantly elevated serum thyroxine levels were seen in 26% of mice immunized with AdTSHR and AdIL10 versus 61% with AdTSHR alone. Levels of thyroid stimulating antibody, but not nonstimulating antibody, were also decreased, and TSHR-specific splenocyte secretion of interferon-gamma in recall assays was impaired in mice treated with AdIL10. In contrast, AdTGF(beta) had little effect on hyperthyroidism. Overall, our findings demonstrate that gene delivery of IL-10, but not TGF-beta, suppresses the induction of Graves' hyperthyroidism in a mouse model. However, the effect of IL-10 is less powerful than we observed previously with T helper type 2-inducers including adenovirus expressing IL-4, Shistosoma mansoni infection or alpha-galactosylceramide.
authors.affiliation: Department of Medical Gene Technology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Saitoh
authors.forename: Y
authors.initials: Y
authors.lastname: Mizutori
authors.forename: N
authors.initials: N
authors.lastname: Takamura
authors.forename: H
authors.initials: H
authors.lastname: Yamasaki
authors.forename: A
authors.initials: A
authors.lastname: Kita
authors.forename: H
authors.initials: H
authors.lastname: Kuwahara
authors.forename: Y
authors.initials: Y
authors.lastname: Nagayama
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage; D006111:Graves Disease / Q000276:immunology*; D018828:Immunoglobulins, Thyroid-Stimulating / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D011485:Protein Binding; D011989:Receptors, Thyrotropin / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology; D014161:Transduction, Genetic / Q000379:methods; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology*
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D018828:Immunoglobulins, Thyroid-Stimulating; D011989:Receptors, Thyrotropin; D016212:Transforming Growth Factor beta; C118905:thyroid stimulation-blocking antibody; D016753:Interleukin-10