Document Detail

Multiple sclerosis: glatiramer acetate inhibits monocyte reactivity in vitro and in vivo.
MedLine Citation:
PMID:  15090474     Owner:  NLM     Status:  MEDLINE    
It is widely assumed that glatiramer acetate (GA), an approved agent for the immunomodulatory treatment of multiple sclerosis, acts primarily as an antigen for T lymphocytes. Recent studies, however, indicated that in vitro, GA directly inhibits dendritic cells, a rare but potent type of professional antigen-presenting cell (APC). To investigate whether these in vitro observations are relevant to the actions of GA in vivo, we studied the effects of GA on monocytes, the major type of circulating APC. In a first series of experiments, we investigated the effects of GA on monocyte reactivity in vitro. Monocytes were stimulated with ligands for Toll-like receptor (TLR)-2 (peptidoglycan and lipoteichoic acid), TLR-4 [lipopolysaccharide (LPS)] and TLR-5 (flagellin), as well as two proinflammatory cytokines (interferon-gamma and granulocyte-monocyte colony-stimulating factor). Monocyte activation was measured by induction of the surface markers signalling lymphocytic activation molecule (SLAM), CD25 and CD69 (detected by cytofluorometry), and by production of monocyte-derived tumour necrosis factor (TNF)-alpha (detected by enzyme-linked immunospot assay). GA had a broad inhibitory effect on all measures of monocyte reactivity, regardless of which stimulator was used. It is unlikely that this reflects a simple toxic effect, because monocyte viability and CD14 expression were unaffected. In a second series of experiments, we investigated the properties of monocytes cultured ex vivo from eight GA-treated multiple sclerosis patients, eight untreated multiple sclerosis patients and eight healthy subjects. We found that LPS-induced SLAM expression and TNF-alpha production were significantly reduced in monocytes from GA-treated patients compared with controls. These results demonstrate for the first time that GA inhibits monocyte reactivity in vitro and in vivo, significantly extending the current concept of the mechanism of action of GA.
Martin S Weber; Michaela Starck; Stefan Wagenpfeil; Edgar Meinl; Reinhard Hohlfeld; Cinthia Farina
Related Documents :
9657324 - Effect of o-antigenic polysaccharide of escherichia coli on endotoxin neutralizing acti...
24043374 - Higher body weight patients on clopidogrel maintenance therapy have lower active metabo...
2160074 - Antiendotoxin activity of lipid a analogues: requirements of the chemical structure.
16378374 - Bis(bibenzyls) from liverworts inhibit lipopolysaccharide-induced inducible nos in raw ...
9203374 - Differential cytotoxic effects induced after photosensitization by hypericin.
3311624 - The role of prostaglandins and allied substances in uterine haemostasis.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-04-16
Journal Detail:
Title:  Brain : a journal of neurology     Volume:  127     ISSN:  0006-8950     ISO Abbreviation:  Brain     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-05-28     Completed Date:  2004-07-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372537     Medline TA:  Brain     Country:  England    
Other Details:
Languages:  eng     Pagination:  1370-8     Citation Subset:  AIM; IM    
Institute for Clinical Neuroimmunology, Marchioninistrasse 15, D-81377 Munich, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Antigens, CD
Cells, Cultured
Cytokines / biosynthesis
Glycoproteins / metabolism
Immunoglobulins / metabolism
Immunosuppressive Agents / pharmacology*,  therapeutic use
Lipopolysaccharides / immunology
Membrane Glycoproteins / immunology
Middle Aged
Monocytes / drug effects*,  immunology
Multiple Sclerosis, Relapsing-Remitting / drug therapy*,  immunology
Peptides / pharmacology*,  therapeutic use
Receptors, Cell Surface / immunology
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptor 5
Toll-Like Receptors
Tumor Necrosis Factor-alpha / biosynthesis
Reg. No./Substance:
0/Antigens, CD; 0/Cytokines; 0/Glycoproteins; 0/Immunoglobulins; 0/Immunosuppressive Agents; 0/Ligands; 0/Lipopolysaccharides; 0/Membrane Glycoproteins; 0/Peptides; 0/Receptors, Cell Surface; 0/TLR2 protein, human; 0/TLR4 protein, human; 0/TLR5 protein, human; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; 0/Toll-Like Receptor 5; 0/Toll-Like Receptors; 0/Tumor Necrosis Factor-alpha; 0/copolymer 1; 169535-43-7/CD150 antigen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Idiopathic partial epilepsy with auditory features (IPEAF): a clinical and genetic study of 53 spora...
Next Document:  Neural correlates associated with impaired disgust processing in pre-symptomatic Huntington's diseas...