Effects of experimental hyper- and hypothyroidism on natural defense activities against Lewis lung carcinoma and its spontaneous pulmonary metastases in C57BL/6 mice.

The effects of expermentally induced hyper- and hypothyroidism on the growth and development of spontaneous pulmonary metastases of Lewis lung carcinoma (3LL) cells were studied in a murine system. Progression of 3LL tumors growing in mice was associated with significant reduction in the serum levels of T3 and T4. Subcutaneous (s. c.) injections (3 times/week) of T3 resulted in a hyperthyroid state with elevated T3 and reduced T4, whereas treatment with T4 induced a hyperthyroid state with elevated T3 and T4 levels. On the other hand, treatment with methimazole induced hypothyroidism with reduced T3 and T4 levels. Under these experimental conditions, treatment with T3 significantly inhibited spontaneous pulmonary metastases, and prolonged survivals of the mice. Methimazole suppressed primary and metastatic tumor growth and prolonged survival. In contrast, treatment with T4 enhanced primary tumor growth and development of pulmonary metastases of 3LL cells. Alveolar macrophages showed enhanced cytotoxicity against 3LL tumor cells after injections of thyroid hormones (T3 and T4) for 4 weeks. The NK activities of spleen cells of mice treated with T4 or methimazole were much lower than those of control mice, and were not affected by treatment with T3. These results imply that changes in thyroid functions may have important influence on natural host defenses against primary and metastatic lung cancer in humans.