Immunology and Oxidative Stress in Multiple Sclerosis: Clinical and Basic Approach

Table 1

Therapeutic strategies for multiple sclerosis.

Immunomodulator agent	Therapeutic action
Aire protein	Modulates the expression of tissue-specific antigens [33, 34].
Interferon-𝛽	INF-𝛽 inhibits proinflammatory cytokines (TNFα, IL-6, IL-𝛽, and IL-17) and T-cell proliferation and clinically reduces the annual rate of relapsing [64, 65].
CD28	Binds to B7.1 (CD80) and B7.2 (CD86). CD4(+)CD28null T cells+ have been found in peripheral blood of patients with MS. These cells produce high levels of IFN-𝛾 and are less susceptible to regulatory mechanisms [44–46].
Inducible costimulator protein	Binds to B7H and modulates Th1/Th2 cytokine production [44–46].
CD40	CD40 is involved in the induction of IL-6 and subsequent IL-17 production [47].
PD-L1	Regulator of T-cell response [44–46].
CD58 mRNA	Increases the expression of Foxp3 transcriptional factor in Treg cells [48].
Foxp3	Regulator gene in Treg cells and determines its role in the maintenance of homeostasis and self-tolerance [39].
CD39 and CD73	Potent molecules involved in regulating IL-17 toxicity suppression [28, 49].
T cells expressing 𝛾𝛿 phenotype	Provides a first line of defense against infections, through the secretion of IFN-𝛾. Clonally expanded 𝛾𝛿 T cells were found in acute MS brain lesions [4].
𝛾𝛿 cells	Source of cytokine in innate immunity and exhibit a potential influence on adaptive immune responses. In models of EAE have both protective and pathogenic roles [4].
TGF-𝛽	It has suppressive effects on both T- and B-cell-related immunity. The selective suppressive effects of TGF-𝛽1 on proinflammatory cytokines such as IFN-y, TNF-𝛼, and LT support a potential role for drugs that upregulate TGF-𝛽 in diseases with prominent Th1 immune response [58–62].
IL-17	Potent proinflammatory cytokine. IL-17 induces the activation of enzyme matrix metalloproteinase-3 and recruits neutrophils to the site of inflammation [63].
Paraoxonase	Enzyme able to hydrolyze preformed oxidized lipids. Exerts a protective role against oxidative damage of cells and lipoproteins [66].
Dietary polyunsaturated fatty acids	Decrease the serum levels of TNFα, IL-1𝛽, IL-6, and nitric oxide catabolites of patients [67].
Uric acid, 𝛼-tocopherol, ascorbate, carotenoids, and glutathione	Free radical scavengers [68].
Transcription factor nuclear factor-E2-related factor (Nrf2)	Binds the antioxidant response element in various promoter regions, which increases the transcription of a variety of cytoprotective genes [69].
NFκB	Upregulates proinflammatory gene expression [70].
Glutathione peroxidase	Antioxidant enzyme that scavenges hydrogen peroxide in the presence of reduced glutathione. Inhibits cytokine-induced NFκB activation [71, 72].