IL-17 – Margaret's Corner

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.

Haematologist appointment. Stefano and I went to see my haematologist at noon today. I asked her outright to classify me. She said that I am definitely not MGUS, no way. My IgGs are too high, and let’s not forget the 40% bone marrow biopsy result (from last year). So it’s official: I’m "smouldering," which means, among other things: "to exist in a state of suppressed activity." Heh. She examined my tests more in detail and pronounced me stable. Stable as a rock. So, all good news.

I asked her what the half-life of a myeloma cell is. She replied that it depends on a variety of factors, such as the type of myeloma and its proliferation rate. It can be calculated using cells from a BMB. She told me that a myeloma cell can live up to several months. MONTHS? Drat, now I am almost sorry I asked!

She confirmed that I am taking the correct amount of vitamin D. She also told me NOT to stop taking curcumin when I get a cold or an infection of any sort. Even though it inhibits NF-kB, she said that stopping cold turkey (odd expression, that one, when you think of it) is not a good thing. Good to know.

Let’s see. I am going down my list of questions and scribbles right now, not necessarily in order of importance. Oh, speaking of importance, this is exciting: I gave her the myeloma stem cell study (she had read the abstract, not the full study) and the DMAPT study, and she is going to find out about the DMAPT trial that should be starting soon in the UK to see if I qualify for it. She is going to contact the researchers that she knows personally. I am at a loss for words. Can’t wait to hear back from her. Gulp!

She is going to push the lab technicians to get more details on my “old” bone marrow samples, which would be fantastic. And, last but not least, she is going to try to attend the upcoming presentation in Calenzano, where I will be giving a brief speech. She is leaving for a conference in Turkey that evening, so it’s iffy. Even if she isn’t able to make it, however, she is sending five people from her lab to the presentation. Five? Fabulous.

Last but not least. For the first time, she wrote that I am stable "perhaps" due to curcumin. And that I should continue with the same treatment. (When my GP read those two sentences this afternoon, he got very excited.)

As we stood up to leave at the end of the visit, she asked me to explain why there are cases of myeloma in India, if curcumin is so effective. I answered that there are only a handful of cases compared to the Western world, and besides, I managed to add with a straight face, those folks undoubtedly didn’t use turmeric in their diet. My husband let out a snort, and she gave me a big smile and shooed us out of her office. Hehe. I love my haematologist. Good sense of humour.

Yes, today was a good day.

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 31^st 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. Oh, and tomorrow is "medical day." I am seeing my haematologist at noon (with a list of questions as long as the highway between Florence and Bologna), then my family doctor in the afternoon (shorter list of questions). I imagine I will have quite a long post tomorrow!