February 5 2008 post. About a month ago I read a Science Daily article with an intriguing title: “Protein’s New Role Discovered In Autoimmune Disease.” (see: http://tinyurl.com/yrzaud). In a nutshell, University of Alabama researchers identified a previously unknown effect of a T cell-derived cytokine named interleukin-17, or IL-17 for short. This is an “immunity protein,” that helps induce and mediate pro-inflammatory responses, such as allergies, autoimmune diseases and whatnot. IL-17 also induces the production of many other cytokines, such as the infamous IL-6! Uh-oh!
Now, the news reported in Science Daily is that when the “messenger” signals from IL-17 were blocked, the disease-causing B cells dropped from 17 to 2 percent. Coincidence? Ah, no. As the articles states, “The drop was a clear sign that IL-17 plays a major role on shaping B cells’ ability to create more and more disease-causing antibodies.” So if IL-17 can be inhibited, B cells are slowed down in their efforts to create wacky antibodies. And here I thought B cells were the good guys, the cells that defend us against infections etc. Well, in autoimmune diseases they can go bonkers, as we can read in the Science Daily article.
After reading this article, I immediately checked out if IL-17 is involved in myeloma. Of course it is. Hah, figures! For instance, see the abstract of this 2006 study (http://tinyurl.com/2786gs), which shows that IL-17 “is a CD4 T-cell-derived mediator of angiogenesis that stimulates vascular endothelial cell migration and regulates the production of a variety of proangiogenic factors, such as tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial cell growth factor (VEGF).” Need I add more? Oh, ok, just this bit: the researchers conclude that “IL-17 plays a role in the promotion of angiogenesis and associated disease progression in MM.” Bad, bad IL-17!
I found an interesting bit of information on IL-17 in the MD Anderson October 31st 2005 “Weekly News and Notes for Patients, Families and Visitors.” The article is titled “New immune cell found to be a key to inflammatory diseases” (see: http://tinyurl.com/2moorw). MD Anderson and other researchers discovered a new type of T-cell, called THi, produced IL-17, which they “linked to an immune system gone awry." An awry immune system? Well, if that doesn’t sound familiar…! Before this discovery, IL-17 was known to play a role in autoimmune and inflammatory diseases, but its origin was a mystery. The study’s lead investigator stated that “These findings suggest that shutting down the activity of these THi cells might stop chronic inflammatory diseases from developing in the first place.” How about that?
Okay, IL-17 is now officially on my list of evil pro-inflammatory cytokines. It is also connected, by the way, to NF-kB (I need to do more research on this topic; I may get to it, someday…). IL-17 also stimulates IL-8, which is an angiogenesis cytokine in myeloma. This reminds me that one of my future projects is to create a permanent page listing all of these pro-inflammatory cytokines and their role in myeloma progression. Eh.
I would like to end today with a question: is there anything that we can do to inhibit IL-17? Or could we already be doing something? The answer to this question will be in tomorrow’s post.
February 6 2008 post: Well, the answer to yesterday’s question is as follows: yes, we can. Curcumin inhibits IL-17. Figures, huh? There are three (possibly more) studies that mention the IL-17-inhibiting role of curcumin. The abstracts can be viewed here: http://tinyurl.com/2rn3jy (a 2003 study), http://tinyurl.com/ynvkdj (a 2005 study). Thanks to Sherlock, I read the full study of the third abstract, a 2004 study published in “Cellular Signaling” and titled, get this: “Interleukin-17 signal transduction pathways implicated in inducing matrix metalloproteinase-3, -13 and aggrecanase-1 genes in articular chondrocytes” (see abstract: http://tinyurl.com/2lfy7t).
All these studies tell us that curcumin inhibits IL-17. Simple as that.
I just read an article that I THINK is related to this (although I could be wrong – I’m not yet a MM guru). If you google “Curcumin for the prevention of progression in monoclonal gammopathy of undetermined significance: A word of caution (Review)” it is the first article, a .pdf. I wonder if you’ve heard of this downside at all? I’m wondering how real the concern actually is (or isn’t).
Hi Jessica, I sent you a message privately but had to leave one here, too. I wrote about this so-called “study” some time ago. Last March, in fact. Like you, I was concerned…at first. But, as you can read in my last (and final!) post on the matter (April 1st), this “study” is built on fluff. And it made me hopping mad, in fact. See: http://margaret.healthblogs.org/2010/04/01/about-to-leave-for-rome%e2%80%a6and-a-few-random-thoughts%e2%80%a6/
I mean, if the authors are so concerned about the inhibition of IL-12, how come they didn’t also write about the perils of using conventional drugs, such as dexamethasone and thalidomide, which inhibit IL-12 much MUCH more strongly than curcumin? Outrageous.
As far as I am concerned, the case is closed.
I don’t mean to sound harsh (as I mentioned, and as is obvious from my April 1 post, this “study,” once I realized how ridiculous it was, drove me nuts)…This was a good find on your part. 🙂 So please keep looking. Research is soooo important for us (patients), and I don’t have the time or resources to find everything that has ever been published, of course. So I rely on my blog readers a lot!
In sum, and to answer your question, there is zero concern.
Hi Margaret,lately I wondered wether the gamopathies
MM and WM have some auotoimmune component. If so,I enclose here a non scientific article about cetyl myristoleate and ask if one of the readers knows more about the general mechanisms of this substence.
click on Google’s cetyl myristoleate and immunomodulation, then please read
Immunomodulator New treatment for arthritis
by Cidney Judd
Dear Margaret, I discovered your blog very recently. It’s very interesting and you’re doing a very lovely and helpful job!
I’m from Bergamo, near Milan.
In May, my mother (64 y.o.) was diagnosed with Myeloma multiple st.III. Now she’s doing the 2nd cycle of chemoteraphy. I’m very interested in the use of curcumin: it’s the first time I’ve heard about it.
In your opinion, is it possible for her to take it while doing the chemoteraphy?
my mother is very tired, and her strenght often fail her.
Thank you again for you reply