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thefireorgan wrote:I know that BG-12 is thought to reduce Th2 cells thereby balancing out with Th1 cells and I believe I have read that LDN has a similar effect in increasing Th1 cells

• Fumarates improve multiple sclerosis (MS) and psoriasis, two diseases in which both IL-12 and IL-23 promote pathogenic T helper (Th) cell differentiation. However, both diseases show opposing responses to most established therapies. First, we show in humans that fumarate treatment induces IL-4-producing Th2 cells in vivo and generates type II dendritic cells (DCs) that produce IL-10 instead of IL-12 and IL-23. In mice, fumarates also generate type II DCs that induce IL-4-producing Th2 cells in vitro and in vivo and protect mice from experimental autoimmune encephalomyelitis. Type II DCs result from fumarate-induced glutathione (GSH) depletion, followed by increased hemoxygenase-1 (HO-1) expression and impaired STAT1 phosphorylation. Induced HO-1 is cleaved, whereupon the N-terminal fragment of HO-1 translocates into the nucleus and interacts with AP-1 and NF-κB sites of the IL-23p19 promoter. This interaction prevents IL-23p19 transcription without affecting IL-12p35, whereas STAT1 inactivation prevents IL-12p35 transcription without affecting IL-23p19. As a consequence, GSH depletion by small molecules such as fumarates induces type II DCs in mice and in humans that ameliorate inflammatory autoimmune diseases. This therapeutic approach improves Th1- and Th17-mediated autoimmune diseases such as psoriasis and MS by interfering with IL-12 and IL-23 production.

Effect of FAE on T-Cells
One of the first observations during the application of Fumaderm® in psoriasis was the effect on T-cells. Initial studies revealed a decrease of T-cells in nearly all treated patients [2]. This finding was well in line with an immunohistochemical study that showed a reduction of CD4+-cells by half [5] in the epidermal inflammatory infiltrate. Subsequent in vitro studies confirmed the capability of DMF to induce apoptosis in human T-cells [26]. Upon analysis of the cytokine production in more detail, de Jong et al. [6] reported that MMF increased the production of the “TH2” cytokines interleukin (IL)-4 and IL-5 in stimulated T-cells without having an effect on the “TH1” cytokine interferon gamma (IFN-γ), the IL-2 production, or the proliferation of T-cells. In another study, stimulated CD4+CD45RO+ memory T-cells again showed an increased secretion of IL-4 and IL-5 after treatment with MMF. Taken together, these findings suggest that FAE shift the cytokine profile from a “TH1” to a “TH2” profile. This effect of FAE on the expression of cytokines may also apply to other cell types than T-cells.