Longitudinal interferon-β effects in multiple sclerosis: Differential regulation of IL-10 and IL-17A, while no sustained effects on IFN-γ, IL-4 or IL-13

Interleukin-17A Levels Vary in Relapsing-Remitting Multiple Sclerosis Patients in Association with Their Age, Treatment and the Time of Evolution of the Disease

“…On the other hand, IL-10 levels were elevated in MS patients, being higher in those who are in remission. IL-10 is an immunomodulatory cytokine with predominantly suppressive actions that is produced by many cell types including T reg cells [26]. Previous studies indicate that treatment with IFN-β or GA induces elevated IL-10 production [27,28,29], which enhances the immunomodulatory effect in the remission phase in our patients.…”

IFN-β differentially regulates the function of T cell subsets in MS and EAE

“…Accordingly, IFN-βtreatment of PBMCs from MS patients also lessened IL-17 mRNA and protein levels, but whether this effect was direct on Tcells was not addressed in this study [66]. Recently, Kvarnström performed a longitudinal study and reported that IFN-β treatment of MS patients for one year decreased IL-17 production by PBMCs [67]. Additionally, IFN-βreduced in vitro the proportion of CD4 + IL-17A + and CD4 + IL-17F + T cells from MS patients' PBMCs, while decreased in vivo gene expression of IL-17C and IL-23R in PBMCs from IFN-βtreated MS patients [63].…”

“…Thorough investigation of the molecular mechanisms that underlie the beneficial effects of type I IFNs on each T cell subtype would be crucial for understanding the possibility of designing novel customized IFN-β-based therapies that selectively target and manipulate specific T cell subpopulation, thus possibly improving existing therapeutic interventions in MS. Expression of Th1 chemokines and their receptors on CD4 + T in the CNS [54] IFN-γ production by Th1 cells [53] ↓ ↓ ↑ Expression of T-bet and IFN-γ genes in the blood [43] CCR5 mRNA levels and its ligands on T cells [56] CCR5, IL-12Rβ2 and IFN-γ mRNA levels in PBMCs [57] Th17 ↓ ↓ ↓ IL-17 production by MOG-primed splenocytes [51] Frequency of CD4 + IL-17 + LN cells on day 4 of EAE [58] Frequency of CD4 + IL-17 + and CD4 + CCR6 + splenocytes and IL-17 production on day 10 of EAE [62] ↓ ↓ ↓ ↑ ↓ IL17 production by MOG-primed LN cells [28] IL17 mRNA levels in spleen and LN cells [37,64] Frequency of CD4 + IL-17 + cells in the brain [38] Production of IL-27 by DCs [38] Expression of Th17 chemokines and their receptors on CD4 + T cells in the CNS [54] ↓ IL-17A and IL-17F production by CD4 + T cells in PBMCs [63] ↓ ↓ ↓ ↓ Th17 cells differentiation in PBMCs [61,65] IL-17 mRNA and protein levels in PBMCs [66,67] Proportion of IL-17A + and IL-17F + CD4 + T cells in PBMCs [63] Expression of IL17C and IL23R genes in PBMCs [63] Tregs ↑ ↑ ↑ IL-10 production by splenocytes [28] IL-10 mRNA levels in PLP-specific T cells and IL-10 protein in PLP-primed LN cells [40] Treg proliferation [72] ↑ IL-10 and Foxp3 mRNA levels in serum and CSF [80] ↑ ↑ ↑ ↑ ↑ Treg function and proportion in peripheral blood [73] IL-10 mRNA and protein levels in PBMCs [40,82] IL-10 production by CD4 + T cells in PBMCs [65] IL-10 + cells in PBMCs [67,…”

“…Regarding the human disease, in vitro treatment of PBMCs from MS patients with IFN-β enhanced the expression of IL-10mRNA and protein [40,82]. Moreover, IFN-β administered to MS patients augmented IL-10 mRNA and protein levels in serum and CSF [67,80]. A very important finding was that, although previous studies did not identify whether the effect of IFN-β was direct on T cells or mediated via modulation of bystander cells, Ramgolam et al detected a direct increase of IL-10 production by CD4 + T cells, isolated from MS patients and treated with IFN-βin vitro [65].…”

Cytokines in Multiple Sclerosis – Possible Targets for Immune Therapies

“…These include IL-10, IL-12, IL-17F, IL-23, IL-27, etc. [2,10,[12][13][14]. The cerebro-spinal fluid (CSF) IL-10 was found increased in MS patients, treated for two years with IFN-beta-1a but not with placebo.…”