Effects of IFN-β1a and IFN-β1b treatment on the expression of cytokines, inducible NOS (NOS type II), and myelin proteins in animal model of multiple sclerosis

Abstract

The aim of this study was to investigate the effects of interferon (IFN)-β1a and IFN-β1b treatment on inflammatory factors and myelin protein levels in the brain cortex of the Lewis rat experimental autoimmune encephalomyelitis (EAE), animal model of multiple sclerosis. To induce EAE, rat were immunized with inoculums containing spinal cord guinea pig homogenized in phosphate-buffered saline and emulsified in Freund’s complete adjuvant containing 110 µg of the appropriate antigen in 100 µl of an emulsion and additionally 4-mg/ml Mycobacterium tuberculosis (H37Ra). The rats were treated three times per week with subcutaneous applications of 300,000 units IFN-β1a or IFN-β1b. The treatments were started 8 days prior to immunization and continued until day 14 after immunization. The rats were killed on the 14th day of the experiment. EAE induced dramatic increase in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-concentrations and inducible nitric oxide synthase (iNOS) expression in the brain, which closely corresponded to the course of neurological symptoms and the loss of weight. Both IFN-β1b and IFN-β1a treatments inhibited the pro-inflammatory cytokines (IL-6, IL-1β, TNF-α and IFN-γ), decreased the activation of astrocytes, increased the myelin protein level in the brain cortex, and improved the neurological status of EAE rats by different mechanisms; IFN-β1a reduced iNOS expression, at least in part, by the enhancement of IL-10, while IFN-β1b diminished IL-10 concentration and did not decrease EAE-induced iNOS expression.

Shikonin ameliorates Experimental Autoimmune Encephalomyelitis (EAE) via Immuno-modulatory, anti-apototic, and anti-oxidative activity

“…Our results showed that Shikonin greatly delayed incidence and reduced mean clinical score in the mouse model of EAE. In the present study, the expression level of TNF-α, IL-6, and IFN-γ were reduced in EAE group, which were consistent with previous reports (23,24). TNF-α has a direct role in the induction of oligodendrocytes demyelination, apoptosis and the loss of oligodendrocyte progenitor cells (25,26), so the enhancement in the percent of demyelination observed in the EAE group may partly due to the elevated TNF-α gene expression which was reduced in Shikonin treated group.…”

Hypomethylation of the Interferon <i>γ</i> Gene as a Potential Risk Factor for Essential Hypertension: A Case-Control Study

“…IFN-γ enhances the class I antigen presentation pathway, induces the replacement of constitutive proteasome subunits in the CD8 + T cell population, and independently clears infection and damaged cells of the endothelium as a part of CD8 + T cell homeostasis (Denton et al 2011). Accumulating evidence indicates that IFN-γ, the first cytokine identified in endothelial cells, induces the expression of major histocompatibility complex genes and enhances the antiviral activity of immune cells (Lubina-Dąbrowska et al 2017). Furthermore, some studies revealed that the methylation of proinflammatory-cytokine genes is associated with blood pressure, e.g., genes of C-reactive protein, IL-6, IL-1 beta (IL-1β), and tumor necrosis factor α (Sullivan et al 2007;Lópezjaramillo et al 2008;Bay-Richter et al 2012;Mao et al 2017b).…”

Shikonin ameliorates experimental autoimmune encephalomyelitis (EAE) via immunomodulatory, anti-apoptotic and antioxidative activity

“…In this study, the expression levels of TNF-a, IL-6 and IFN-c were reduced in the EAE group, which were consistent with previous reports. [28,29] TNF-a has a direct role in the induction of oligodendrocytes demyelination, apoptosis and loss of oligodendrocyte progenitor cells, [30,31] so enhancement in the percentage of demyelination which was observed in the EAE group may be partly due to the elevated TNF-a gene expression which was reduced in the shikonin-treated group. IFN-c is another pro-inflammatory cytokine with an activating role in the process of inflammation in EAE and MS, the overexpression of which in the CNS causes progressive demyelinating diseases.…”