We aimed to assess the Carvacrol effects on clinical manifestations and production of pro-inflammatory (IFN-γ, IL-6 and IL-17) and anti-inflammatory (TGF-β, IL-4, and IL-10) cytokines in experimental autoimmune encephalomyelitis (EAE) as MS animal model.
Ly6G<sup>+</sup> cells were recruited to the CNS during experimental autoimmune encephalomyelitis (EAE), interacted with B cells that produced the cytokines GM-CSF and interleukin-6 (IL-6), and acquired properties of PMN-MDSCs in the CNS in a manner dependent on the signal transducer STAT3.
The data showed that acute attack of EAE in DA rats was followed by accumulation of IL-6, TGF-β1 and MTs proteins, by increased expression of MTs in molecular and granular cell layer, by reduced expression of gp96/granular cell, by apoptosis and by microgliosis with appearance of Iba-1+ cells, co-expressing MT I/II and gp96.
These findings suggest that LH2171 might down-regulate IL-6 production and the subsequent Th17 differentiation and spinal cord infiltration, consequently alleviating EAE symptoms.
Deficiency of the G protein Gαq ameliorates experimental autoimmune encephalomyelitis with impaired DC-derived IL-6 production and Th17 differentiation.
Based on a number of adjuvant-induced experimental models, IL-6 is critical to the development of autoimmune diseases including experimental autoimmune encephalomyelitis, adjuvant-induced arthritis, and experimental autoimmune myocarditis.
Collectively, these findings indicate that decreased miR-497 expression is responsible for IL-17-triggered high HIF-1α expression and consequent IL-1β and IL-6 production by astrocytes in EAE mice.Cellular & Molecular Immunology advance online publication, 1 May 2017; doi:10.1038/cmi.2017.12.
To further prove IL-6 to be responsible for the control of inflammation during EAE through gp130 on macrophages/neutrophils, we immunized LysMcre<sup>pos</sup>IL-6R<sup>loxP/loxP</sup> mice.
Adoptive transfer of Tcell lines from IL-6+/+ mice induced EAE in the mice with the intact IL-6 gene but less in the IL-6-deficient mice, indicating that the resistant phenotype cannot be explained solely by lack of encephalitogenic Tcells.
Physical exercise inhibited the production of inflammatory cytokines, such as IFN-γ, IL-17 and IL-1β in the spinal cord after EAE induction, as well as spleen cells obtained from ST group showed a significant upregulation of regulatory T cell markers, such as CD25 and IL-10 levels, and blocked IL-6, MCP-1 and TNF-α production, mainly, during acute and chronic phase of EAE.
In this research, an IL6-associated miRNA, miR26a, was identified, and its normally downregulated expression was shown to be highly correlated with disease severity in patients suffering from MS as well as in C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE; a well-established animal model of human MS).
In addition, naringenin promoted Treg polarization and also prevented IL-6-induced suppression of Treg development via down-regulation of p-Smad2/3 as well as inhibition of IL-6 signaling, and the latter was further supported by the <i>in vivo</i> results showing lower soluble IL-6R but higher soluble gp130 levels in plasma of naringenin-fed compared to the control EAE mice.
In C57BL/6 mice with EAE, PCB orally improved clinical status of the animals and reduced the expression levels of brain IL-6 and IFN-γ proinflammatory cytokines.
The severe EAE developed by Hx(-/-) mice could be ascribed to an enhanced expansion of Th17 cells accounting for both a higher disposition of naive T cells to differentiate toward the Th17 lineage and a higher production of Th17 differentiating cytokines IL-6 and IL-23 by APCs.
Taking these data together, we conclude that IL-6 secretion is a major mechanism of B cell-driven pathogenesis in T cell-mediated autoimmune disease such as EAE and MS.