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

Eur J Immunol. 1996 Sep;26(9):2067-74. doi: 10.1002/eji.1830260916.


Type 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 microM 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)-gamma 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-gamma production by purified CD4+CD45RO+ (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-gamma secretion, MMF again appeared to induce high levels of IL-4 and IL-5 secretion while IFN-gamma production was unaffected. These results may be relevant for the development of therapeutic regimens designed to correct inappropriate Th1 subset development in immunopathologic conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fumarates / pharmacology*
  • Humans
  • Immunologic Memory
  • Interleukin-4 / biosynthesis*
  • Interleukin-5 / biosynthesis*
  • Leukocyte Common Antigens / analysis
  • Lymphocyte Activation / drug effects
  • Maleates / pharmacology*
  • Psoriasis / drug therapy*
  • Sheep
  • Th2 Cells / drug effects*
  • Th2 Cells / immunology


  • Fumarates
  • Interleukin-5
  • Maleates
  • citraconic acid
  • Interleukin-4
  • Leukocyte Common Antigens