Interleukin-18 induces insulin resistance in the hyperthyroid state.

We previously reported that serum interleukin-18 (IL-18) levels were significantly increased in hyperthyroid Graves' disease patients. The development of insulin resistance in hyperthyroidism has been documented. We investigated the relationship between IL-18 and insulin resistance in patients with hyperthyroid Graves' disease and in experimental hyperthyroid mice. Then, we examined whether IL-18 induces insulin resistance in mice injected with IL-18 for a week. A significant positive correlation was observed between serum IL-18 levels and parameters such as thyroid functions and homeostasis model assessment for insulin resistance in hyperthyroid Graves' disease. In experimental hyperthyroid mice, IL-18 was significantly elevated. Insulin resistance increased in experimental hyperthyroid mice and IL-18-injected mice. These findings suggest IL-18 to be an important factor inducing insulin resistance in hyperthyroidism.