Diminished production of type-I interferons and interleukin-2 in patients with multiple sclerosis

Abstract

Several lines of evidence have supported the role of immunological mechanisms in the pathogenesis of multiple sclerosis (MS) and new immunomodulatory strategies for its treatment, e.g. subcutaneous application of interferon (IFN)-beta, have emerged. We investigated the ability of peripheral blood mononuclear cells (PBMC) in 21 consecutive patients with clinically definite MS to produce interferons and lymphokines in response to viral or mitogenic stimulation. Ten patients showed clinical signs of disease activity (acute relapse) and 11 patients were in a stable condition. Additionally, white blood count, leukocyte differentiation and lymphocyte subtyping were performed. A group of age-related healthy blood donors served as control (n=20). There was no difference between patients and controls in the production of IFN-gamma, tumor necrosis factor (TNF)-alpha and soluble interleukin (IL)-2 receptor. IFN-alpha and IFN-beta responsiveness, however, was significantly lower in patients with stable disease than in patients with active disease and controls (p<0.001). Furthermore, secretion of IL-2 after stimulation was significantly diminished in both patient groups as compared to the control group (p<0.01). Analysis of T-cell subsets revealed a significantly lower amount of CD8+ T-cells in patients with stable disease, leading to a significantly higher CD4/CD8 ratio in this group as compared to patients with active disease. Our study depicted an IL-2 deficiency in MS patients which is shared with other autoimmune diseases. In addition, our findings suggest that the ability to produce type-I IFNs, IFN-alpha and IFN-beta, is primarily impaired in MS patients and changes in correlation to the course of disease activity.

The Influence of Typical and Atypical Neuroleptic Drugs in the Production of Interleukin-2 and Interferon-Gamma in vitro

“…The most consistent findings were decreased levels of the T-cell cytokines IL-2 [1][2][3][4][5][6][7] as well as increased levels of the soluble IL-2 receptor [8,9] in a whole blood assay of schizophrenic patient samples after stimulation with phytohemagglutinin (PHA). These results resemble findings in autoimmunologic diseases such as rheumatoid arthritis [10] or multiple sclerosis [11] and therefore support the hypothesis that immunologic factors contribute to the pathogenesis of schizophrenia. The decreased levels of IL-2 and IFN-Á after stimulation in whole blood assays of schizophrenic patients might be due to a genetic predisposition of the cytokine-producing cells, a reduced production capacity after excessive pro-duction (e.g.…”

Identification of the Synthetic Cannabinoid R(+)WIN55,212-2 as a Novel Regulator of IFN Regulatory Factor 3 Activation and IFN-β Expression

“…Indeed a defect in IFN-␤ production has been reported in immune cells from MS patients (39). PBMCs isolated from healthy subjects were responsive to poly(I⅐C) with an increase in IFN-␤ mRNA observed, whereas R(ϩ)WIN55,212-2 ablated this (Fig.…”

Mitochondria as Oxidative Signaling Organelles in T-cell Activation: Physiological Role and Pathological Implications

“…A crucial role of PKCh for T-cell-specific CD95L expression was also documented (Kaminski et al 2007;Manicassamy and Sun 2007). Underlining the role of complex I-derived ROS for IL-2 expression, T cells of MS patients were reported to be defective in activation-induced IL-2 secretion (Wandinger et al 1997). In addition, UCP2-deficient mice are known to be more prone to EAE development (Vogler et al 2006).…”