In this study, the following methods were used for investigating the effects of LA on long-term EAE: hematoxylin-eosin staining (HE) and electron microscopic examinations of pathological changes; Western blotting of β-amyloid precursor protein (β-APP) and myelin basic protein (MBP); Enzyme-linked immunosorbent assay (ELISA) of tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), superoxide dismutase (SOD), malondialdehyde (MDA) as well as flow cytometry of CD4+CD25+FoxP3+ regulatory T cells (Tregs).
In a murine relapsing experimental allergic encephalomyelitis (EAE) model, gene therapy to block TNF was investigated with the use of a retroviral dimeric p75 TNF receptor (dTNFR) construct.
The serum measures of myeloperoxidase (MPO), nitric oxide (NO) as well as splenocytes-originated pro-inflammatory interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α) were significantly decreased in EAE rats treated by 17β-ED primed-MSCs compared to EAE rats that received untreated MScs.
Extensive studies in the animal model experimental autoimmune encephalomyelitis have suggested that multiple sclerosis is an autoimmune disorder mediated by myelin-specific CD4 T cells secreting T helper type 1 cytokines and tumor necrosis factor alpha.
TNF blockade during acute EAE in GFAPγR1Δ both limited OLG apoptosis and enhanced OPC differentiation consistent with reduced lesion size and clinical recovery.
Treatment of EAE mice with GL from onset to the peak stage of disease resulted in marked attenuation of EAE severity, reduced inflammatory cell infiltration and demyelination, decreased tumor necrosis factor-alpha (TNF-α), IFN-γ, IL-17A, IL-6, and transforming growth factor-beta 1, and increased IL-4 both in serum and spinal cord homogenate.
EAE mice with hMSC treatment on day 3 and day 12 had: (1) lower serum levels of IL-6, TNF-α (p < 0.0005), and IL-17 (p < 0.005 for day 3, p < 0.0005 for day 12); (2) reduced splenic cell production and secretion of IL-6, TNF-α (p < 0.05), and IL-17 (p < 0.05), and increased splenic production of IL-10; (3) reduced splenic Th17 cells (p < 0.05 for day 3, p < 0.005 for day 12), and (4) increased CD1d(high)CD5(+) regulatory B cells (p < 0.005) compared to EAE mice without hMSC treatment.
Gene expression study showed that DAB(389)IL-2 treatment suppressed TNF-α and IFN-γ as well as IL-10 cytokine gene expression in the spinal cord of rats with EAE on day 13.
In vitro, after blocking the IL-33, the proliferation of primary astrocytes, the production of MCP-1/CCL2 and TNF-α by astrocytes, and the production of TNF-α by primary microglia stimulated by the homogenate of the peak stage of EAE were increased.
TNF-γ values were increased in experimental autoimmune encephalomyelitis mice relative to normal, but were not altered by opioid growth factor or low-dose naltrexone.
On the other hand, while TNF-deficient mice are protected from EAE, anti-TNF antibodies worsen the disease in MS patients, suggesting caution in extrapolating preliminary basic studies to the patient.
Included conditions for re-analysis of differentially expressed genes (DEGs) were MS, myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) in rats, proteolipid protein-induced EAE in mice, Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), and a transgenic tumor necrosis factor-overexpressing mouse model (TNFtg).
Moreover, monocyte-autonomous TNF is critical for the function of these cells, as <i>TNF</i> ablation in monocytes/macrophages, but not in microglia, delayed the onset of EAE in challenged animals and was associated with reduced acute spinal cord infiltration of Ly6C<sup>hi</sup> effector monocytes.
Interferon gamma (IFN-γ)/tumor necrosis factor alpha (TNF-α) and interleukin-4 (IL-4)/interleukin-10 (IL-10), the hallmark cytokines that direct Th1 and Th2 development, were detected with enzyme-linked immunosorbent assay (ELISA). terminal dUTP nick-end labeling (TUNEL) staining was performed to elucidate the cell apoptosis in the spinal cords of EAE mice.
Experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis (MS) was induced by the myelin oligodendrocyte glycoprotein (MOG), whose effects were quantified by examining the changes in: clinical score, lipid peroxidation products, carbonylated proteins, glutathione system, tumor necrosis factor alpha (TNFα), and lipopolysaccharide membrane bacteria (LPS).
Based on these observations, we conclude that unlike TNF, which promotes autoimmune inflammation, TRAIL inhibits autoimmune encephalomyelitis and prevents activation of autoreactive T cells.
In FABP7-knockout (KO) mice, the onset of EAE symptoms occurred earlier than in wild type (WT) mice, and mRNA expression levels of inflammatory cytokines (IL-17 and TNF-α) were higher in FABP7-KO lumbar spinal cord than in WT lumbar spinal cord at early stage of EAE.
Recently, it has been reported that the TNF receptor (TNFR) II plays an essential role in the pathology and progression of experimental autoimmune encephalomyelitis, an animal model of MS. To investigate whether TNFR II polymorphisms influence susceptibility and/or clinical progression of MS, genomic DNA of 321 samples of the Austrian Genetics in MS study group and DNA of 174 platelet donors, who served as healthy controls, were genotyped for five polymorphic sites in the TNFR II gene: exon 6 nucleotide (nt) 676*T-->G, exon 6 nt 783*G-->A (both are associated with non-conserved amino acid substitution), exon 10 nt 1663*G-->A, exon 10 nt 1668*T-->G, and exon 10 nt 1690*T-->C (all of which are located in the 3' non-coding region of the gene).