Document Detail


Selective stimulation of T helper 2 cytokine responses by the anti-psoriasis agent monomethylfumarate.
MedLine Citation:
PMID:  8814248     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
R de Jong; A C Bezemer; T P Zomerdijk; T van de Pouw-Kraan; T H Ottenhoff; P H Nibbering
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of immunology     Volume:  26     ISSN:  0014-2980     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  1996 Sep 
Date Detail:
Created Date:  1996-10-24     Completed Date:  1996-10-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  2067-74     Citation Subset:  IM; X    
Affiliation:
Department of Immunohematology and Bloodbank, University Hospital Leiden, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD45 / analysis
Fumarates / pharmacology*
Humans
Immunologic Memory
Interleukin-4 / biosynthesis*
Interleukin-5 / biosynthesis*
Lymphocyte Activation / drug effects
Maleates / pharmacology*
Psoriasis / drug therapy*
Sheep
Th2 Cells / drug effects*,  immunology
Chemical
Reg. No./Substance:
0/Fumarates; 0/Interleukin-5; 0/Maleates; 207137-56-2/Interleukin-4; 498-23-7/citraconic acid; EC 3.1.3.48/Antigens, CD45

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