Curative treatment of experimental autoimmune thyroiditis by in vivo administration of plasmid DNA coding for interleukin-10.
The autoimmune response in experimental autoimmune thyroiditis (EAT) is characterized by a lymphocyte infiltration of the thyroid gland and by the appearance of circulating autoantibodies to thyroglobulin (Tg). Cytokines play a crucial role in the immunoregulation and pathology of EAT. Systemic administration of IL-10 has curative effects on EAT, but requires high doses and 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 lymphocytic infiltration in the thyroids. A significant diminution in the proliferative anti-Tg T cell response was observed, along with a trend towards 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 therapy using non-viral vectors is a novel and promising approach for the treatment of thyroid autoimmune disorders.
Batteux
F
F
Laboratoire d'Immunologie, Faculté de Médicine Cochin-Port Royal, Paris, France.
Trebeden
H
H
Charreire
J
J
Chiocchia
G
G
D000818:Animals; D004337:Drug Carriers; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics*; D015847:Interleukin-4 / Q000276:immunology; D008081:Liposomes; D051379:Mice; D008808:Mice, Inbred CBA; D010957:Plasmids; D013601:T-Lymphocytes / Q000276:immunology; D013954:Thyroglobulin / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000628:therapy*
D004337:Drug Carriers; D008081:Liposomes; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D013954:Thyroglobulin