Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
Balance of Th1/Th2 cytokines in thyroid autoantibody synthesis in vitro.
Autoimmunity. 1999;30(1):1-9. Unique Identifier : AIDSLINE MED/99360471 Guo J; Rapoport B; McLachlan SM; Cedars-Sinai Research Institute and the University of California,; Los Angeles School of Medicine, 90048-1869, USA.
Abstract:
Thyroid-infiltrating lymphocytes spontaneously synthesize IgG class thyroid autoantibodies while blood lymphocytes require activation to produce the same autoantibodies. Surprisingly, the stimulus commonly used to induce autoantibodies by blood lymphocytes, Pokeweed mitogen (PWM), inhibits autoantibody synthesis by thyroid lymphocytes. To address this dichotomy, we investigated the Th1: Th2 cytokine balance in relation to thyroid peroxidase (TPO) autoantibody production in cultures of thyroid, lymph node and blood lymphocytes. The characteristic PWM effect on TPO autoantibody production by thyroid and blood lymphocytes (10 day cultures) was confirmed. Cytokine measurements in these cultures revealed that PWM increased IFN-gamma production by thyroid, lymph node and blood lymphocytes. However, PWM enhanced IL-4 levels in lymphocytes from blood and lymph node but not in thyroid lymphocytes. Moreover, the IL-4: IFN-gamma ratios in short- and long-term cultures were higher for PBMC and lymph node lymphocytes than for thyroid lymphocytes. In summary, PWM shifts the cytokine balance towards Th2 for blood lymphocytes and towards Th1 for thyroid lymphocytes. The shift towards Th1 in the target organ is associated with reduced autoantibody synthesis. Our observations suggest that "immune deviation" towards Th2 as a form of therapy in Graves' disease could project the patient from the frying pan into the fire.
Keywords: JOURNAL ARTICLE Autoantibodies/*BIOSYNTHESIS/BLOOD Enzyme-Linked Immunosorbent Assay Graves' Disease/BLOOD/*IMMUNOLOGY Human Interferon Type II/ANALYSIS/SECRETION Interleukin-4/IMMUNOLOGY/SECRETION Iodide Peroxidase/IMMUNOLOGY Lymph Nodes/SECRETION Lymphocytes/SECRETION Pokeweed Mitogens/IMMUNOLOGY/PHARMACOLOGY Support, U.S. Gov't, P.H.S. Thyroid Diseases/BLOOD/*IMMUNOLOGY Thyroid Gland/SECRETION Thyroiditis, Autoimmune/BLOOD/*IMMUNOLOGY Th1 Cells/IMMUNOLOGY/SECRETION Th2 Cells/IMMUNOLOGY/SECRETION 991130
A99B1069
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