Selective stimulation of T helper 2 cytokine responses by the anti‐psoriasis agent monomethylfumarate

Abstract

AbstractType 2 cytokines are thought to have a protective role in psoriasis vulgaris by dampening the activity of T helper 1 (Th1) lymphocytes. The aim of the present study was to determine the effect of monomethylfumarate (MMF), the most active metabolite of the new anti‐psoriatic drug Fumaderm®, on the production of cytokines and the development of Th subsets. MMF was found to enhance interleukin (IL)‐4 and IL‐5 production by CD2/CD8 monoclonal antibody‐stimulated peripheral blood mononuclear cells (PBMC) in a dose‐dependent manner. Maximal effects of MMF were found at a concentration of 200 μM and resulted in tenfold enhanced levels of IL‐4 and IL‐5 production. MMF did not affect the levels of IL‐2 production, interferon (IFN)‐γ production or proliferative T cell responses in these cultures. Similar effects of MMF were observed in cultures of purified peripheral blood T cells indicating that this compound can act directly on T cells. MMF did not influence cytokine production by purified CD4+CD45RA+ (unprimed) T cells, but greatly enhanced IL‐4 and IL‐5 production without affecting IFN‐γ production by purified CD4+CD45R0+ (primed) T cells. Furthermore, MMF also augmented IL‐4 and IL‐5 production in established Th1/Th0 clones that were stimulated with CD2/CD28 monoclonal antibody. Finally, when PBMC were challenged with Mycobacterium tuberculosis that typically induces Th1 recall responses with strong IFN‐γ secretion, MMF again appeared to induce high levels of IL‐4 and IL‐5 secretion while IFN‐γ production was unaffected. These results may be relevant for the development of therapeutic regimens designed to correct inappropriate Th1 subset development in immunopathologic conditions.