Interferon beta induces interleukin‐10 expression: Relevance to multiple sclerosis

Abstract

Interferon-beta decreases the relapse rate, relapse severity, progression of neurological disability, and development of new brain lesions observed with brain magnetic resonance imaging in relapsing-remitting multiple sclerosis patients. The mechanism of action of this effect is presently unknown. This study was based on the hypothesis that immunoregulatory effects of interferon-beta may underlie its demonstrated clinical efficacy. The objective of the study was to determine the effect of interferon-beta-1a on the expression of interleukin-10, a cytokine that strongly inhibits cell-mediated immune responses. Interferon-beta-1a induced accumulation of interleukin-10 messenger RNA and protein secretion by cultured peripheral blood mononuclear cells. The observed in vitro effects were similar for healthy control subjects and multiple sclerosis patients. Intramuscular injections of interferon-beta-1a increased serum levels of interleukin-10 at 12 and 24 hours following the injection. Greater increases were induced with 12 x 10(6)-IU than 6 x 10(6)-IU injections. The effect of interferon-beta-1a was relatively specific for interleukin-10, as treatment with interferon-beta-1a did not result in accumulation of transforming growth factor-beta messenger RNA. Upregulation of interleukin-10 represents a possible mechanism of action of interferon-beta's therapeutic effect in relapsing-remitting multiple sclerosis, and has implications for therapy of other autoimmune diseases.

Effects of NS1 variants of H5N1 influenza virus on interferon induction, TNFα response and p53 activity

“…IFNb is capable of promoting expression of a variety of cytokines and chemokines, including IL10, RANTES(CCL5), MCP-1(CCL2), MCP-3(CCL7), MCP-2(CCL8), MIG(CXCL9) and IP-10(CXCL10). [26][27][28] Because an elevated expression of cytokines and chemokines has been proposed to contribute to the unusual severity and mortality of H5N1 infection, 29,30 our results provide evidence in support of the hypothesis that the high pathogenicity of H5N1 virus may be associated with a reduced repression on IFN production conferred by the D92E mutation.…”

Cytokine changes during interferon-beta therapy in multiple sclerosis: Correlations with interferon dose and MRI response

“…Given the potential benefits of increased IL-10 and potential harm of IL-12, several groups have reported improvements in the ratio of IL-10 to IL-12 with IFN-β treatment (Correale et al, 1995,Rudick et al, 1996,Wang et al, 2000,Byrnes et al, 2002, Berghella et al, 2005, Ersoy et al, 2005. We confirmed these prior reports of overall improved ratios of serum IL-10/ IL-12p70 with IFN-β treatment and found that ratios of serum IL-10/IL-12p70 decreased in non-responders to therapy compared to pre-treatment.…”

“…IFN-β has been shown to decrease clinical and MRI measures of disease activity in MS (Interferon Beta Study Group 1993, Paty et al, 1993,PRISMS 1998,Simon et al, 1999. IFN-β acts to increase IL-10 levels and reduce IL-12 levels in MS patients, thus improving the ratio of IL-10 to IL-12 (Correale et al, 1995,Rudick et al, 1996,Wang et al, 2000,Byrnes et al, 2002, Berghella et al, 2005, Ersoy et al, 2005. The mechanism of IL-12 suppression has been shown to depend on IL-10 induction (Wang et al, 2000).…”

Altered phenotype and function of blood dendritic cells in multiple sclerosis are modulated by IFN-βand IL-10

“…Decreased IL-10 and increased IL-12 p40 mRNA are associated with disease activity [29]. IFN-b treatment influences cytokine levels with increasing Th2 cytokine production [30,31] and decreasing proinflammatory Th1 cytokine production [32].…”