Adenovirus-mediated gene delivery of interleukin-10, but not transforming growth factor β, ameliorates the induction of Graves’ hyperthyroidism in BALB/c mice

Abstract

Summary Interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) are well known anti-inflammatory cytokines. We have studied the effect of adenovirus-mediated IL-10 and TGF-β 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 AdTGFβ) 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 AdTGFβ, 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-γ in recall assays was impaired in mice treated with AdIL10. In contrast, AdTGFβ had little effect on hyperthyroidism. Overall, our findings demonstrate that gene delivery of IL-10, but not TGF-β, 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 α-galactosylceramide.