More recently, Jin et al.[81] studied the possible neuroprotective action of IFN-β against the toxicity induced by LPS-activated microglia on cortical neurons in vitro. They report that IFN-β drastically suppressed the neurotoxic production of superoxide and glutamate by activated microglia, and thereby prevented microglia-induced neuronal cell death.[81] In contrast, there are many studies on the effect of GA on microglia.

GA was developed to mimic a major component of the myelin sheath, myelin basic protein, and its beneficial immunomodulatory effects are not completely understood, albeit apparently related to modulation of antigen-presenting cells

that affect effector T-cell and B-cell responses, as well as regulatory T cells.[82] Although the Enzalutamide nmr exact mechanism of GA is not clear, the many studies conducted both in EAE and MS indicate that GA modulates the function of both adaptive and innate immune system cells directly or indirectly, promoting a less pro-inflammatory environment. Kim et al.[83] postulated that GA exerts its effect also through the induction of type 2 antigen-presenting cells, which preferentially mediate T helper type 2 cell differentiation, and showed in an ex vivo study that GA-reactive T cells isolated from GA-treated MS patients this website promote an alternatively activated phenotype in human microglia. Tolmetin Exposure to the supernatant of GA-reactive T cells before or after initiation of GA therapy modulated human microglia differentially, promoting a classically or alternatively activated phenotype, respectively.[83] In contrast, Pul et al.[84] addressed the possibility that GA also has a direct effect on microglia

in vitro. They observed an induction of the alternatively activated phenotype in primary LPS-activated rat microglia cultures exposed to GA, with down-regulation of TNF-α and up-regulation of IL-10, together with an increase in phagocytic activity perhaps mediated through an IL-10 autocrine loop.[84] Gentile et al.[85] showed through in vivo and ex vivo electrophysiological studies and confocal microscopy analysis that the beneficial effect of GA on EAE-induced glutamate synapse dysfunction is related to a direct effect on microglia, promoting the alternatively activated phenotype in these cells, with inhibition of TNF-α release, which has been shown to exert a direct detrimental effect on synapses.[86] They report that GA treatment led to a reduction in microglia proliferation and to a modulation of the classically activated phenotype, with microglial cells of a resting morphology being observed in the striatum of EAE-affected GA-treated mice.