Research: glatiramer acetate inhibits monocyte reactivity

A board to discuss the Multiple Sclerosis modifying drug Copaxone

Research: glatiramer acetate inhibits monocyte reactivity

Postby Arron » Sun Apr 25, 2004 1:49 pm

Another study on Copaxone's possible mode of action-- again, we didn't think this was important (or clear enough) to post on the front page, but it's very useful for those investigating Copaxone.

Multiple sclerosis: glatiramer acetate inhibits monocyte reactivity in vitro and in vivo.

Weber MS, Starck M, Wagenpfeil S, Meinl E, Hohlfeld R, Farina C.

Institute for Clinical Neuroimmunology, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany.

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.

PMID: 15090474 [PubMed - as supplied by publisher]
User avatar
Arron
Volunteer Moderator
 
Posts: 892
Joined: Sun Feb 01, 2004 3:00 pm
Location: California, USA

Advertisement

Return to Copaxone

 


  • Related topics
    Replies
    Views
    Last post

Who is online

Users browsing this forum: No registered users


Contact us | Terms of Service