TY - JOUR
T1 - Newer insights into the pathogenesis of experimental autoimmune thyroiditis
AU - Stafford, E. A.
AU - Rose, N. R.
N1 - Funding Information:
This study was supported by PHS NIH research grant HL33878 and training grant ES07141.
PY - 2000
Y1 - 2000
N2 - Experimental autoimmune thyroiditis (EAT), produced in the mouse by immunization with murine thyroglobulin plus complete Freund's adjuvant, represents a valuable model for studying the pathogenesis of human chronic (Hashimoto's) thyroiditis. A major issue requiring clarification is the difference between benign autoimmunity, characterized solely by production of autoantibodies to thyroglobulin, and pathogenic autoimmunity where injury occurs to the thyroid cells. In this article, we describe the role of two key cytokines, IL12 and IFNγ, in modifying the pathogenic immune response. EAT, defined by cellular infiltration of the thyroid and the development of thyroglobulin-specific autoantibodies, is a dynamic process. Consequently, a cytokine may exert a different effect at different times during the disease process. For purposes of discussion, we propose that there are three stages in the development of EAT: priming; initiation; and progression. Administration of anti-IL12 during the priming stage and initiation dramatically decreases disease and lowers autoantibody levels. In contrast, injection of recombinant IL12 after disease was established significantly decreases the severity of disease and reduces autoantibody levels. Unlike IL-12, IFNγ was not essential for the priming of EAT. However, the severity of disease in the anti-IFNγ-treated initiation-and progression-treated animals was higher than in controls, implying a regulatory role for IFNγ. These findings emphasize that EAT involves a complex array of pathogenic mechanisms. The balance of cytokines produced during the early phase of the autoimmune reaction probably determines the progression from a harmless autoimmune response to autoimmune disease.
AB - Experimental autoimmune thyroiditis (EAT), produced in the mouse by immunization with murine thyroglobulin plus complete Freund's adjuvant, represents a valuable model for studying the pathogenesis of human chronic (Hashimoto's) thyroiditis. A major issue requiring clarification is the difference between benign autoimmunity, characterized solely by production of autoantibodies to thyroglobulin, and pathogenic autoimmunity where injury occurs to the thyroid cells. In this article, we describe the role of two key cytokines, IL12 and IFNγ, in modifying the pathogenic immune response. EAT, defined by cellular infiltration of the thyroid and the development of thyroglobulin-specific autoantibodies, is a dynamic process. Consequently, a cytokine may exert a different effect at different times during the disease process. For purposes of discussion, we propose that there are three stages in the development of EAT: priming; initiation; and progression. Administration of anti-IL12 during the priming stage and initiation dramatically decreases disease and lowers autoantibody levels. In contrast, injection of recombinant IL12 after disease was established significantly decreases the severity of disease and reduces autoantibody levels. Unlike IL-12, IFNγ was not essential for the priming of EAT. However, the severity of disease in the anti-IFNγ-treated initiation-and progression-treated animals was higher than in controls, implying a regulatory role for IFNγ. These findings emphasize that EAT involves a complex array of pathogenic mechanisms. The balance of cytokines produced during the early phase of the autoimmune reaction probably determines the progression from a harmless autoimmune response to autoimmune disease.
KW - Cytokines
KW - IFN-γ
KW - IL-12
KW - Thyroglobulin
KW - Thyroiditis
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U2 - 10.3109/08830180009088510
DO - 10.3109/08830180009088510
M3 - Article
C2 - 11129113
AN - SCOPUS:0034517363
SN - 0883-0185
VL - 19
SP - 501
EP - 533
JO - International Reviews of Immunology
JF - International Reviews of Immunology
IS - 6
ER -