F. Batteux et al., Curative treatment of experimental autoimmune thyroiditis by in vivo administration of plasmid DNA coding for interleukin-10, EUR J IMMUN, 29(3), 1999, pp. 958-963
The autoimmune response in experimental autoimmune thyroiditis (EAT) is cha
racterized by a lymphocyte infiltration of the thyroid gland and by the app
earance of circulating autoantibodies to thyroglobulin (Tg). Cytokines play
a crucial role in the immunoregulation and pathology of EAT. Systemic admi
nistration of IL-10 has curative effects on EAT, but requires high doses an
d iterative injections due to the rapid turnover of this molecule. We have
designed an original in vivo gene transfer using a mixture of liposomes and
poly-L-Lysine that greatly enhanced the transfection yield, and induced a
fast and long-lasting expression of IL-10 on mouse thyroid follicular cells
(TFC). IL-10 expression on TFC of mice wit EAT dramatically wipe out the l
ymphocytic infiltration in the thyroids. A significant diminution in the pr
oliferative anti-Tg T cell response was observed, along with a trend toward
s a Th2 response characterized by decreased production of IFN-gamma and by
increased anti-Tg IgG1/IgG2a Ab ratios. In conclusion, local IL-10 gene the
rapy using non-viral vectors is a novel and promising approach for the trea
tment of thyroid autoimmune disorders.