INTRATHYROIDAL CYTOKINE GENE-EXPRESSION PROFILES IN AUTOIMMUNE-THYROIDITIS

Cytokines are thought to mediate the initiation and perpetuation of au toimmune thyroiditis. However, this concept is mainly based on in vitr o findings and to date only interleukin (IL)-6 and interferon-gamma (I FN-gamma) have been detected in Graves' disease in vivo. The cytokine pattern produced by T-helper (Th) cells has important regulatory effec ts on the nature of the immune response. We therefore determined these cytokine mRNAs in Graves' disease and Hashimoto's thyroiditis. RNA wa s extracted by cesium chloride gradient centrifugation from the thyroi d tissue of 12 patients undergoing thyroid resection for Graves' disea se and from two patients being treated for Hashimoto's thyroiditis. Tw o patients with parathyroid adenomas and one patient with a goiter wer e used as controls. RNA was also extracted from normal human thyroid e pithelial cells in primary culture. The cDNAs were prepared by reverse transcription and amplified for IL-2, -4, -5, -6 and -10 and IFN-gamm a by polymerase chain reaction. All the cytokine mRNAs were detected i n the Hashimoto's thyroid glands in large quantities. Six of the 12 Gr aves' disease thyroid glands showed, when compared with controls, an i ncreased accumulation of transcripts for: IFN-gamma, IL-2, -4 and -10 or IL-2, -4 and IFN-gamma or IL-2 and IFN-gamma or IFN-gamma alone, ea ch in one case or IL-2 alone in two cases. These cytokine profiles wer e not representative of a Th1 or Th2 phenotype. Increased amounts of c ytokine mRNA in thyroid glands from Graves' disease patients were most ly associated with high microsomal antibody titres and/or prominent in trathyroidal lymphocytic infiltration. IL-6 and/or IL-10 mRNAs were de tectable in all Graves' disease thyroid glands and in control thyroid tissue. IL-10 mRNA was not detectable in normal human thyroid epitheli al cells in primary culture. Graves' disease and Hashimoto's thyroidit is clearly differ with respect to the number of positive intrathyroida l cytokine mRNAs and their levels. The different cytokine patterns in Graves' disease and in Hashimoto's thyroiditis could reflect the clini cal spectrum of autoimmune thyroiditis which is characterized by thyro id tissue destruction and/or thyroid autoantibody production. These da ta suggest that the course of autoimmune thyroiditis is regulated by t he interplay of several cytokines.