Anti-Malarials for control of autoimmunity

A
Thomé et al. Chloroquine Treatment Enhances Regulatory T Cells and Reduces the Severity of Experimental Autoimmune Encephalomyelitis. PLoS One. 2013;8(6):e65913. Print 2013.

BACKGROUND: The modulation of inflammatory processes is a necessary step, mostly orchestrated by regulatory T (Treg) cells and suppressive Dendritic Cells (DCs), to prevent the development of deleterious responses and autoimmune diseases. Therapies that focused on adoptive transfer of Treg cells or their expansion in vivo achieved great success in controlling inflammation in several experimental models. Chloroquine (CQ), an anti-malarial drug, was shown to reduce inflammation, although the mechanisms are still obscure. In this context, we aimed to access whether chloroquine treatment alters the frequency of Treg cells and DCs in normal mice. In addition, the effects of the prophylactic and therapeutic treatment with CQ on Experimental Autoimmune Encephalomyelitis (EAE), an experimental model for human Multiple Sclerosis, was investigated as well.

METHODOLOGY/PRINCIPAL FINDINGS: EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG35-55) peptide. C57BL/6 mice were intraperitoneally treated with chloroquine. Results show that the CQ treatment provoked an increase in Treg cells frequency as well as a decrease in DCs. We next evaluated whether prophylactic CQ administration is capable of reducing the clinical and histopathological signs of EAE. Our results demonstrated that CQ-treated mice developed mild EAE compared to controls that was associated with lower infiltration of inflammatory cells in the central nervous system CNS) and increased frequency of Treg cells. Also, proliferation of MOG35-55-reactive T cells was significantly inhibited by chloroquine treatment. Similar results were observed when chloroquine was administrated after disease onset.

CONCLUSION: We show for the first time that CQ treatment promotes the expansion of Treg cells, corroborating previous reports indicating that chloroquine has immunomodulatory properties. Our results also show that CQ treatment suppress the inflammation in the CNS of EAE-inflicted mice, both in prophylactic and therapeutic approaches. We hypothesized that the increased number of regulatory T cells induced by the CQ treatment is involved in the reduction of the clinical signs of EAE.



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MouseDoctor

6 comments

  • Sorry for the rubbish post…not sure what I was thinking of…."Maybe cure of the week" could be a Gin and Tonic for the next treatment fad.

    Chloroquine is taken at about7mg/kg a week as an anti-malaria.

    Will it be a useful adjunct for MS treatment…who would fund the study? The effect is not like you can achieve with say FTY720 (drug in fingolimod =formulated FTY720)

    Anyway my posts are just stocking fillers/appetizers for the main prezzie/main course by the Boss….who gets the interesting posts of relevance to do.

    ProfG always writes virtually all of the top ten posts….maybe because he lobs more intellectual-hand grenades.

    I suspect this post will not get up there

  • Dr. Mouse, I read your work. This blog is a rich resource and it would have much less depth and substance without your writing.

  • MD,

    Has chloroquine been tried in MS before? I know it's been used in lupus for years, presumably due to some immune effect… Not sure how efficacious though.

    • Yes in 1963 it was tried without any postive effect
      http://www.ncbi.nlm.nih.gov/pubmed/14063049

      Whether this was a group of MSers who would never respond to immunotherapy remains to be established and is quite possible. This work was not cited in the current paper.

      Chloroquine has been used in Lupus as you say and one problem was a side effect of damage to vision. So would it get developed for MS. It was used in 1963 so there is no inventive step, Would it be worth risking a few million dollars for this…..I would doubt it.

  • Interesting, in that another widely used antimalarial, artemisinin, has also recently been shown to be effective in treating autoimmune diseases (lupus nephritis in particular). The formula for artemisinin was discovered on the wall of an ancient Chinese tomb in the 1970s. Artemisinin is now the most used antimalarial in the world. It's also been shown to be effective against cancer cells in vitro, and appears to have antiviral properties as well.

    Unfortunately, another promising candidate that will never find the funding for proper clinical trials…

    All you might ever want to know about artemisinin:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758403/

  • Lupus is thought to be a problem of anti-DNA antibodies and MS may be on the other side of the spectrum of autoimmunity.

    Its amazing what you find on walls. It is not always "Kilroy woz ere"

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