Abnormalities of in vitro production of interleukin-1 and interleukin-2 in Graves' disease

Abstract

In order to investigate abnormalities of cytokine production in Graves' disease, we measured ability of mononuclear cells (PMC) obtained from patients with Graves' disease and healthy subjects to produce interleukin-1 (IL-1) and interleukin-2 (IL-2) activities. The effects of anti-thyroid drugs on the production of IL-1 and IL-2 in PMC of healthy subjects were also examined. Both IL-1 and IL-2 activities in culture supernatants were determined by radioimmunoassay. When monocytes purified from PMC were stimulated with lipopolysaccharide (LPS), IL-1 release in culture supernatants was significantly higher in Graves' disease patients with hyperthyroid function compared with in healthy subjects and the patients with euthyroid function. IL-2 production in phytohemagglutinin (PHA)-stimulated PMC culture was significantly lower in Graves' disease patients with hyperthyroid function than in healthy individuals. Methimazole (MMI) and propilthiouracil (PTU) suppressed the LPS-induced IL-1 production in monocytes from healthy subjects in a dosedependent manner. MMI enhanced PHA-induced IL-2 production in PMC from healthy subjects, whereas PTU had no effects. Triiodothyronine (T₃) enhanced IL-1 production in two of four normal subjects in repeated experiments, suggesting that there exists heterogeneity of the effects of T₃ among individuals. Thus, it is expected that these abnormal findings of increased IL-1 and decreased IL-2 production observed in Graves' disease patients with hyperthyroid function will be futher modified by thyroid hormone and administration of anti-thyroid drugs.