The influence of 6-mercaptopurine and aminopterin was studied on immune response and immune thyroiditis in guinea pigs immunized with thyroid extract.

1. Both compounds depressed delayed hypersensitivity to thyroglobulin and immune thyroiditis.

2. Antibody formation to thyroglobulin was strongly depressed by aminopterin but not significantly influenced by 6-mercaptopurine.

3. Immune response and thyroiditis were suppressed as long as the compounds were administered; after discontinuation of treatment, immune response and thyroiditis appeared in the same time intervals as observed in control animals after initiation of immunization.

4. Treatment with 6-mercaptopurine and aminopterin 10 days after immunization lead to suppression of delayed hypersensitivity and thyroiditis.

5. Treatment with 6-mercaptopurine of animals after onset of thyroiditis lead to suppression of delayed hypersensitivity and disappearance or diminution of round cell infiltration in the thyroid.

6. The results are discussed in terms of the pathogenesis of experimental immune thyroiditis, the mode of action of these antimetabolites on this experimental immune disease, and in view of the potential value of these compounds in human diseases.

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