Saturday, March 19, 2011

Lupus Drugs: Anti-malarials/Plaquenil


            Anti-malarials have been used to treat lupus since the 1950’s. In fact, prior to Benlysta’s approval, the last drug approved for lupus was the anti-malarial plaquinel, which was approved in 1956. My understanding, though it may be incorrect, is that lupus patients who were being treated for malaria noticed an improvement of their lupus symptoms. They reported this improvement, it was studied, and plaquinel was approved. (Interesting side note: Viagra came into existence in much the same way. The molecule used in Viagra was originally being investigated for heart symptoms. It was a serendipitous discovery that it also improved…other symptoms, shall we say?)

            For a long time plaquenil was used without anyone really knowing exactly how it worked. However, recently a biological explanation for how plaquenil helps improve lupus was discovered. It would appear that plaquenil blocks some proteins in the “Toll-like Receptor” (or TLR) family. TLRs are proteins that the cell uses as a first line defense against infection. Each TLR is specific for one thing, and only one thing. Some bind to free-floating DNA, others to various bacterial proteins. If they bind to their molecule of choice, they signal to the cell that an infection is occurring, and the immune response is activated.

In an autoimmune disease like lupus, the normal mechanisms that the immune system uses to sense infection get confused. For example, in a healthy person nucleic acids (such as DNA) are never just floating around in the blood; instead they are neatly packaged up in cells. In an infection, on the other hand, DNA from either dead cells or viruses may get dumped into the blood. The immune system has therefore evolved some TLRs to "see" free-floating DNA as a sign that there’s a problem, and to activate an immune response. Unfortunately, in lupus patients there is often free-floating DNA around because the immune system is attacking the body’s own cells, which are then spilling their DNA into the blood. So the immune system is activated as the TLRs see DNA where it shouldn’t be. Plaquenil helps solve this problem by preventing the TLRs from ever seeing the DNA. This helps keep the immune cells from thinking that there’s an infection, and the inflammatory response is therefore kept down.

So is plaquenil an immunosuppressant? I guess that depends on your definition. It does prevent the immune system from “seeing” DNA floating around in the blood. That means even if there is an infection causing the DNA to be there the immune system will not be able to see it. On the other hand, most immunosuppressants work by actually killing off cells in the immune system, which plaquenil does not do. I would personally not put plaquenil in the immunosuppressant class, but as I said before, it depends on what definition you’re using.


Obviously I have to make generalizations to translate immunology findings into English. For further more technical reading, I recommend the following sources:
http://www.jacionline.org/article/S0091-6749(10)03047-2/fulltext#sec2.1
http://www.ncbi.nlm.nih.gov/pubmed/18220957
http://www.ncbi.nlm.nih.gov/pubmed/20490286
http://en.wikipedia.org/wiki/Toll-like_receptor

26 comments:

  1. What I've read is that it was soldiers who were treated for malaria who also had rheumatoid arthritis that brought plaquenil's usefulness to light. (In those days if you were diagnosed with lupus you were basically dead.) That might well have included your great uncle, by the way, who was a ship's captain serving in the Pacific.

    ReplyDelete
  2. You need to be a part of a contest for one of
    the best blogs on the net. I most certainly will recommend this site!


    Have a look at my page :: singapore condo price

    ReplyDelete
    Replies
    1. Thank you, that's very kind of you. I can barely keep up with it, so I'm just happy when people read it!

      Delete
  3. Hey! Someone in my Facebook group shared this website with us
    so I came to give it a look. I'm definitely enjoying the
    information. I'm book-marking and will be tweeting this to my followers!
    Great blog and fantastic design and style.

    My site :: chainsaw reviews

    ReplyDelete
    Replies
    1. Thanks! Unfortunately, my blog's spam filter blocks any comments that includes links to what looks like advertisements, so most comments are not getting through unless they are from personal email accounts/gmail. So if you don't see your comment here, that's why.

      Delete
  4. This comment has been removed by a blog administrator.

    ReplyDelete
  5. Wow, marvelous weblog layout! How long have you ever been running a
    blog for? you make running a blog look easy. The total glance of your web site is
    excellent, as smartly as the content material!

    My weblog - best compact microwave

    ReplyDelete
    Replies
    1. I've been running a blog for about seven years. I've been running this particular one for...maybe four years?

      Delete
  6. I do not even know how I ended up here, but I thought this post was great.

    I don't know who you are but definitely you are going to a famous blogger if you are not already ;) Cheers!


    Here is my webpage electric knife sharpener reviews

    ReplyDelete
  7. Good day! I just would like to give you a huge thumbs up for the great info you have got right here on this post.
    I'll be returning to your website for more soon.

    My homepage ... best riding lawn mower

    ReplyDelete
  8. Greetings from Los angeles! I'm bored at work so I decided to check out your site on
    my iphone during lunch break. I love the info
    you present here and can't wait to take a look when I get
    home. I'm amazed at how fast your blog loaded on
    my mobile .. I'm not even using WIFI, just 3G .. Anyhow, superb
    site!

    Also visit my website :: best youth baseball bats

    ReplyDelete
    Replies
    1. Thanks! This is what I do in *my* lunch break!

      Delete
  9. Asking questions are actually good thing if you are not understanding something entirely, but this post gives
    good understanding yet.

    my website: best cooler

    ReplyDelete
  10. Have you ever thought about including a little bit more than just your articles?
    I mean, what you say is valuable and all. But think of if you added some
    great graphics or video clips to give your posts more, "pop"!
    Your content is excellent but with pics and videos, this blog could
    certainly be one of the most beneficial in its niche.
    Fantastic blog!

    Have a look at my website; bottle warmer reviews

    ReplyDelete
    Replies
    1. I usually put pictures in my posts, but I'm scared of mosquitoes, which seemed like the most obvious thing to put here. I guess I could put malaria parasites, but not that many people would recognize them!

      Delete
  11. It's perfect time to make some plans for the
    future and it's time to be happy. I have read this post and if
    I could I wish to suggest you some interesting things or
    suggestions. Maybe you could write next articles referring to this article.
    I want to read even more things about it!

    My weblog best car subwoofers

    ReplyDelete
    Replies
    1. What other articles did you have in mind? I'm always open to suggestions.

      Delete
  12. Excellent, what a website it is! This website presents useful facts to us, keep it up.


    my web page: range hood reviews

    ReplyDelete
  13. Saved as a favorite, I like your site!

    Also visit my homepage :: best home coffee maker

    ReplyDelete
  14. Hi! I could have sworn I've visited this site before but after browsing
    through a few of the articles I realized it's new
    to me. Nonetheless, I'm definitely pleased I stumbled
    upon it and I'll be bookmarking it and checking back often!



    My webpage ... best leather cleaner

    ReplyDelete
  15. I like the helpful info you provide in your articles. I'll bookmark your
    weblog and check again here regularly. I'm quite sure I'll learn a
    lot of new stuff right here! Good luck for the next!

    Here is my blog :: flex belt review

    ReplyDelete
  16. Please be aware that if you are using drupal gardens for your website my spam filter will automatically block your comment. I have manually added some that look like they're legit (I hope!), but the default will block you. So if I don't respond, I probably haven't seen your comment.

    ReplyDelete
  17. This comment has been removed by a blog administrator.

    ReplyDelete
  18. Generic drugs are identical to the original drug in all aspects, be it dose, strength or effect. Generic drugs have a hugely competitive market and this in turn is beneficial for the consumers in the form of reduced prices.
    Drug detox

    ReplyDelete