The Production of Immunoreactive α‐and γ‐Interferon by Circulating Mononuclear Cells in Type 1 Diabetes

Abstract

Using a specific immunoradiometric assay method the in vitro alpha interferon response to polyinosinic:polycytidylic acid (poly-I:C) and the gamma interferon response to concanavalin A were measured in peripheral blood mononuclear cells from 11 healthy matched pairs of Type 1 diabetic patients and normal subjects. The alpha-interferon response to poly-I:C was significantly higher in the diabetic group (median 3.7 (range less than 1-25.7) u ml-1) than in the normal group (1.1 (less than 1-15.4) u ml-1, p less than 0.01). The mean gamma-interferon response to concanavalin A was 64.3 +/- 46.9 (+/- SD) u ml-1 in the diabetic patients and 49.4 +/- 18.5 u ml-1 in the normal group (NS). The higher alpha-interferon response to poly-I:C in the diabetic patients was not related to blood glucose concentration, HbA1, age of onset of diabetes, duration of diabetes, or islet cell antibody positivity, and may therefore indicate intrinsic hyper-responsiveness of circulating mononuclear cells in Type 1 diabetes.

Decreased Secretion of Th2 Cytokines Precedes Up-regulated and Delayed Secretion of Th1 Cytokines in Activated Peripheral Blood Mononuclear Cells from Patients with Insulin-Dependent Diabetes Mellitus

“…However, in our patients, we found no correlation between peak levels, total production and/or secretory profile of all Th1 and Th2 cytokines tested and disease duration. These results correspond with other reports [4,6,[8][9][10]12] and suggest that the cytokine profile of IDDM patients is an independent parameter associated with their disease. They also suggest that the aberrant Th1/Th2 secretory profile of these patients is not transient, but represents a long standing perturbation of the immune system which may underlie the association of IDDM and other autoimmune diseases.…”

“…The novel approach demonstrated in this study is supported by data showing IL-2 secretory patterns that differed significantly in the two groups, even though patients and controls were comparable in their peak levels and total production of IL-2. This may also explain why other investigators, who determined the stimulated level of IL-2 as well as IFN-in IDDM patients at earlier time points, reported lower levels of these cytokines [4,7,10,11]. Our results enhance the importance of a comprehensive cytokine analysis, including total secretory capacity and secretory pattern analysis, when compared to the limited peak level determination.…”

“…They also demonstrate that the failure of IDDM patients to mount an early Th2 response results in an uninhibited late increase in Th1. In contrast to previous reports, where cytokine levels in IDDM patients were sampled only once after stimulation [4][5][6][7][10][11][12], we examined stimulated secretion over time. This enabled us to introduce two innovative parameters: cytokine secretory pattern and total cytokine production, and to provide a more comprehensive analysis of the Th1/Th2 imbalance in IDDM patients.…”

“…The plasma levels and stimulated secretion of other cytokines including IFN-, IFN-, TNF-, IL-1 and IL-6 were found comparable in patients and controls [8][9][10]. Berman et al [11], demonstrated that IL-4 secretion from stimulated PBMC and T cells of IDDM patients at onset is reduced in the presence of normal secretion of IL-1 and normal expression of IFN-mRNA.…”

The role of viruses in human diabetes

“…It was later shown that interferon-α was raised when the serum of adult diabetic patients was tested [48]. In more recent studies, increased concentrations of interferon-α were again detected in the blood of a wide group of new and treated Type I diabetic patients, as was interferon mRNA in blood cells.…”