Intrathyroidal cytokine gene expression profiles in autoimmune thyroiditis.
Cytokines are thought to mediate the initiation and perpetuation of autoimmune thyroiditis. However, this concept is mainly based on in vitro findings and to date only interleukin (IL)-6 and interferon-gamma (IFN-gamma) have been detected in Graves' disease in vivo. The cytokine pattern produced by T-helper (Th) cells has important regulatory effects on the nature of the immune response. We therefore determined these cytokine mRNAs in Graves' disease and Hashimoto's thyroiditis. RNA was extracted by cesium chloride gradient centrifugation from the thyroid tissue of 12 patients undergoing thyroid resection for Graves' disease and from two patients being treated for Hashimoto's thyroiditis. Two patients with parathyroid adenomas and one patient with a goiter were used as controls. RNA was also extracted from normal human thyroid epithelial cells in primary culture. The cDNAs were prepared by reverse transcription and amplified for IL-2, -4, -5, -6 and -10 and IFN-gamma by polymerase chain reaction. All the cytokine mRNAs were detected in the Hashimoto's thyroid glands in large quantities. Six of the 12 Graves' disease thyroid glands showed, when compared with controls, an increased 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, each in one case or IL-2 alone in two cases. These cytokine profiles were not representative of a Th1 or Th2 phenotype. Increased amounts of cytokine mRNA in thyroid glands from Graves' disease patients were mostly associated with high microsomal antibody titres and/or prominent intrathyroidal lymphocytic infiltration.(ABSTRACT TRUNCATED AT 250 WORDS)
Paschke
R
R
Service de Génétique Médicale, Faculté de Médecine, Université Libre de Bruxelles, Belgium.
Schuppert
F
F
Taton
M
M
Velu
T
T
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000378:metabolism*; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006111:Graves Disease / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013961:Thyroid Gland / Q000737:chemistry / Q000378:metabolism*; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D017931:DNA Primers; D007376:Interleukin-2; D015848:Interleukin-5; D015850:Interleukin-6; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma