This Is MS - Minocycline Downregulates T-Cell Activity

Minocycline is a tetracycline-class antibiotic that has shown some promise in treating multiple sclerosis. In fact, a trial is currently underway examining the efficacy of minocycline combined with Copaxone.

One of the main questions on the table when looking at the possible efficacy of an antibiotic for the treatment of MS is "how exactly does it help MS?" If it helps via its antibiotic activity, then that points to a (revolutionary) new view of MS as a disease caused or exacerbated by a bacterial pathogen. If however, it works in another fashion, then it speaks to the more accepted model of MS as an auto-immune inflammatory condition.

All that being said, this new study supports the latter explanation. It shows that minocylcine actually has the effect of lowering the activity of microglial cells (microglial cells are the immune system cells of the central nervous system), as had been seen in previous research, but also downregulates the activity of the "killer" T cells (immune system cells that are specifically programmed to kill a certain other type of cell).

Perhaps this is the pathway in which minocycline holds promise for MS... as always, no definitive answers YET in our quest to end this disease, but plenty of well-formed puzzle pieces.

"These results demonstrate that the mechanism of action of minocycline involves not only microglia but also T cells and their subsequent activation of microglia. The capacity of minocycline to down-regulate CD40L on T cells may provide a new means to target the CD40-CD40L pathway, which regulates several inflammatory processes."

Click "read more" for the full abstract....

Full Abstract Text

Leukoc Biol. 2005 Jul;78(1):135-43. Epub 2005 Apr 7.

Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction.

Giuliani F, Hader W, Yong VW. University of Calgary, 3330 Hospital Drive, Calgary, Alberta T2N 4N1, Canada. vyong@ucalgary.ca.

Minocycline, a tetracycline with anti-inflammatory properties, has been reported to down-regulate the activity of microglia, whose activation occurs in inflammatory and degenerative diseases of the central nervous system, such as multiple sclerosis and Alzheimer's disease. In these disorders, a T cell component is also evident, and we have demonstrated previously that the interaction of activated T cells with microglia led to the substantial increase in tumor necrosis factor alpha (TNF-alpha) levels. Here, we report that minocycline decreases TNF-alpha levels produced in human T cell-microglia interaction. This effect is mediated by a direct action of minocycline on the activated T cells and on microglia, which resulted in the decreased ability of T cells to contact microglia. In correspondence, minocycline decreased the expression on T cells of the CD40 ligand (CD40L), a key molecule regulating the contact-mediated interaction of T cells with microglia. These results demonstrate that the mechanism of action of minocycline involves not only microglia but also T cells and their subsequent activation of microglia. The capacity of minocycline to down-regulate CD40L on T cells may provide a new means to target the CD40-CD40L pathway, which regulates several inflammatory processes.

PMID: 15817702 [PubMed - in process]

Abstract can be found here: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15817702&query_hl=3