CURATIVE AND PROTECTIVE EFFECTS OF IL-10 IN EXPERIMENTAL AUTOIMMUNE-THYROIDITIS (EAT) - EVIDENCE FOR IL-10-ENHANCED CELL-DEATH IN EAT

We studied the effects of in vivo administration of rhIL-10 in two mod els of experimental autoimmune thyroiditis (EAT): 1) in EAT induced by injection of mTg emulsified in adjuvant, and 2) in EAT induced by ado ptive transfer of mTg-specific T lymphocytes. Furthermore, we tried to assess both the protective and curative potential of IL-10 in EAT, by administering rhIL-10 either at the time of priming and challenge wit h mTg, or only at the time of challenge. We demonstrated that prolifer ative and cytotoxic responses of splenic cells to mTg were markedly re duced by in vivo rhIL-10 treatment. Cell surface marker studies reveal ed a 40 to 45% reduction in CD4(+) and in CD8(+) lymphoblastoid spleen cells from mice treated with rhIL-10 either in the early or in the la te EAT. The severity of EAT was significantly reduced in mice treated with high-dose rhIL-10, whereas levels of autoantibodies to mTg were n ot altered. Furthermore, when analyzing purified T lymphocytes fron 1 rhIL-10-treated animals, an increase of cells undergoing apoptotic cel l death became evident in the rhIL-10 treated group, as compared with controls. This IL-10-mediated enhancement of activation-induced cell d eath critically depended on the applied therapeutic dose of rhIL-10. T hus, IL-10 exerts beneficial effects on the development and course of EAT through a mechanism that could imply an IL-10-mediated enhancement of activation-induced cell death in T lymphocytes, findings that call for considering IL-10 in the immunotherapy of early-phase and likewis e of already established autoimmune thyroiditis.