In vitro production of interferon-gamma by peripheral blood from patients with Graves' disease, Hashimoto's thyroiditis and rheumatoid arthritis

Abstract

SUMMARY The production of interferon‐gamma (IFN‐γ) by peripheral blood mononuclear cells (PBMC), CD4 cells, or CD8 cells in response to interleukin‐2 (IL‐2) stimulation has been studied; the samples were obtained from 12 healthy control subjects, 19 patients with Graves' disease (10 hyperthyroid and nine euthyroid), 13 patients with Hashimoto's thyroiditis (four hypothyroid and nine euthyroid), and 15 patients with rheumatoid arthritis (11 active and four inactive). A dose of IL‐2 (25 U/ml) was utilized to induce IFN‐γ by PBMC from all four groups. The incremental increase in IFN‐γ values (with IL‐2 stimulation minus without stimulation) was significantly less in PBMC from patients with Graves' disease, Hashimoto's thyroiditis, and rheumatoid arthritis than that in PBMC from control subjects. The values from PBMC in patients with Graves' disease in a euthyroid state were below normal but greater than those from patients with Graves' disease in a hyperthyroid state. The incremental increase in IFN‐γ values from Graves' disease PBMC correlated with the serum TSH values (r=0.622, P < 0.01), but not with thyroid autoantibodies (anti‐thyroid microsomal antibodies, anti‐thyroid microsomal antibodies, nor TSH‐binding inhibitory immunoglobulin activities). The incremental increase in IFN‐γ from PBMC from both control subjects and Graves* disease was correlated with that from CD4 cells (r=0.711, P < 0.01), but not with that from CD8 cells. The production of IFN‐γ in response to IL‐2 from PBMC in Graves' disease correlated inversely with thyroid function, appearing to reflect the very effect of hyperthyroidism in this process. The precise explanation of these phenomena remains unclear. The decreased response of IFN‐γ to IL‐2 stimulation by PBMC from patients with Graves' disease, Hashimoto's thyroiditis, and rheumatoid arthritis seems to be a non‐specific phenomenon occurring in both organ specific autoimmune disease and systemic autoimmune disease. It may be due to a down‐regulation in autoimmune disease of CD4 cells in response to IL‐2, a decreased level of IL‐2 cellular receptors or a decreased receptor affinity, associated increased soluble IL‐2 receptors, or a defect of the intra‐CD4 cellular IL‐2 signal to produce or release IFN‐γ in the conditions studied.

Modulation of human T cell functions by surface sulphydryl groups: differential effects on IL-2 production and responsiveness

“…Oxidation and blockade of serum and cellular thiols is a characteristic of this disease [24,25]. Many aspects of IL-2 biology have been reported as abnormal in rheumatoid arthritis, including IL-2 production [6][7][8][9][10] and responsiveness [6,7,[11][12][13]. Our data on IL-2 production clearly demonstrate that SH group blockade cannot explain all aspects of aberrant immune function in rheumatoid patients.…”

“…Each of these functions has been found to be depressed in cells from patients with rheumatoid arthritis [2][3][4] and, of particular relevance, may be returned to normal control levels following incubation with a SH-reducing agent such as 2-mercaptoethanol [2,5]. We have chosen to investigate the SH sensitivity of some T cell functions involving IL-2 in more detail, since this cytokine is critically associated with the proliferative response and, moreover, both the production of [6][7][8][9][10] and responsiveness to IL-2 are defective in rheumatoid arthritis [6,7,[11][12][13]. …”

Immunomodulatory Properties of Adipose-Derived Stem Cells Treated with 5-Azacytydine and Resveratrol on Peripheral Blood Mononuclear Cells and Macrophages in Metabolic Syndrome Animals

“…The precise mechanisms of these phenomena remain unclear. However, a decreased response of INFNG that is caused by PBMC was also observed in patients with Graves’ disease, Hashimoto’s thyroiditis, and rheumatoid arthritis [ 31 ]. We hypothesize that defects in INFNG synthesis may result from changes in ASC EMS response to different stimuli and might be related to disease activity.…”