SELECTIVE STIMULATION OF T-HELPER-2 CYTOKINE RESPONSES BY THE ANTI-PSORIASIS AGENT MONOMETHYLFUMARATE

Citation
P. Dejong et al., SELECTIVE STIMULATION OF T-HELPER-2 CYTOKINE RESPONSES BY THE ANTI-PSORIASIS AGENT MONOMETHYLFUMARATE, European Journal of Immunology, 26(9), 1996, pp. 2067-2074
Citations number
45
Categorie Soggetti
Immunology
ISSN journal
00142980
Volume
26
Issue
9
Year of publication
1996
Pages
2067 - 2074
Database
ISI
SICI code
0014-2980(1996)26:9<2067:SSOTCR>2.0.ZU;2-O
Abstract
Type 2 cytokines are thought to have a protective role in psoriasis vu lgaris by dampening the activity of T helper 1 (Th1) lymphocytes. The aim of the present study was to determine the effect of monomethylfuma rate (MMF), the most active metabolite of the new anti-psoriatic drug Fumaderm(R), on the production of cytokines and the development of Th subsets. MMF was found to enhance interleukin (IL)-4 and IL-5 producti on by CD2/CD8 monoclonal antibody-stimulated peripheral blood mononucl ear cells (PBMC) in a dose-dependent manner. Maximal effects of MMF we re found at a concentration of 200 mu M and resulted in tenfold enhanc ed levels of IL-4 and IL-5 production. MMF did not affect the levels o f IL-2 production, interferon (IFN)-gamma production or proliferative T cell responses in these cultures. Similar effects of MMF were observ ed in cultures of purified peripheral blood T cells indicating that th is compound can act directly on T cells. MMF did not influence cytokin e production by purified CD4(+)CD45RA(+) (unprimed) T cells, but great ly enhanced IL-4 and IL-5 production without affecting IFN-gamma produ ction by purified CD4(+)CD45R0(+) (primed) T cells. Furthermore, MMF a lso augmented IL-4 and IL-5 production in established Th1/Th0 clones t hat were stimulated with CD2/CD28 monoclonal antibody. Finally, when P BMC were challenged with Mycobacterium tuberculosis that typically ind uces Th1 recall responses with strong IFN-gamma secretion, MMF again a ppeared to induce high levels of IL-4 and IL-5 secretion while IFN-gam ma production was unaffected. These results may be relevant for the de velopment of therapeutic regimens designed to correct inappropriate Th 1 subset development in immunopathologic conditions.