From SMM to MM: IL-1 beta

February 1 2009 post. I found out about this wonderful little gem from a couple of myeloma list friends (thank you both so very much, D & D!). It’s an editorial (see: http://tinyurl.com/b7z59z) on a Mayo Clinic study titled “Targeting the Pathogenic Role of Interleukin 1beta in the Progression of Smoldering/Indolent Myeloma to Active Disease,” (abstract: http://tinyurl.com/acqlkb; full study: http://tinyurl.com/akqd4r). I haven’t read the full study yet (I will read it tomorrow…it requires more attention and care than I can give it at the moment: ). Both can be found in the February 2009 Mayo Clinic Proceedings. At any rate, I am basing my post on the editorial (shorter and easier to read than the full study…).

 

47 patients, all at the inactive or smouldering myeloma stage (=my stage) but at high risk of progression, participated in the Mayo study, which was carried out between 2002 and 2007. The idea was to answer the fundamental question: WHAT THE HECK makes folks progress from inactive to active myeloma?

 

Apparently what happens is that IL-1beta, another of those beastly pro-inflammatory and pro-angiogenic cytokines, induces marrow stromal cells to produce large amounts of interleukin 6 (IL-6), thereby promoting the survival and expansion of the myeloma cells

 

The researchers confirmed their theory that reducing the activity of IL-1beta does, in fact, significantly increase progression-free survival (PFS) in these high-risk patients. This is extraordinary!

 

And now read this: blocking IL-1beta reduces IL-6 as well as the proangiogenic chemokine IL-8, therefore the use of IL-1beta-blocking strategies may result in new standards of therapy for high-risk patients with SMM/IMM. WOWIE!!!

 

In the study, all the smouldering myeloma patients were given anakinra, an IL-1beta inhibitor that is used for the treatment of rheumatoid arthritis and autoinflammatory diseases. I should add that 25 patients were also given a low dose of dexamethasone. Two of the them remained stable for about four years, and in fact, at the time of this writing, progression to active disease has not yet occurred […]. Since, as I mentioned, I haven’t yet read the actual study, I don’t know what happened in the other 23 cases…

 

Another significant excerpt from the editorial: In the study, patients with a decrease in CRP levels were more likely to have stable disease, confirming that effectively blocking IL-1beta (using CRP levels as the marker for IL-1beta activity) can halt progression to active myeloma.

 

Halt progression to active myeloma…aaaaah, how sweet those five little words sound…

 

Hmmm, but WHY am I so excited that I could skip and dance all around my study (probably will, as soon as I post this)?

 

Because, drum roll!, CURCUMIN INHIBITS IL-1BETA!!! (See, e.g.: http://tinyurl.com/b7yr3j and http://tinyurl.com/bgqud4) There are heaps of studies on this topic, in fact, probably much much better than the above two that I found after a lightning search…but right now I am too elated and, well, in a bit of a hurry–it’s almost dinnertime–to see if I can find the perfect one…I just want to go ahead and post this bit of good news!

 

More good news: curcumin is not the only one. Here is a list of the other natural IL-1beta inhibitors that I have found thus far (ah, but my quest has only just begun, so there will probably be more…):

 

1.     quercetin (strongly) http://tinyurl.com/dfy39r and http://tinyurl.com/c6v3np

2.     omega-3 http://tinyurl.com/c2ksmg

3.     genistein http://tinyurl.com/cbtpsr

4.     EGCG http://tinyurl.com/andmdj

5.     resveratrol http://tinyurl.com/cmnayw

6.     ellagic acid (on my to-be-tested list) http://tinyurl.com/bgvutf

 

UPDATE February 5 2009 post: The list of plant extracts and foods that inhibit IL-1 beta is overwhelming, even more so when you consider that it is composed only of the items that I have been able to think of and look up thus far, in my snippets of time…how many more are there?!

 

The following, therefore, is probably only a partial list of foods (and/or their compounds) that inhibit IL-1 beta. It is intended mainly for those who don’t take supplements for one reason or another. I should note that I frequently found more than just one study per food/food compound:

 

Garlic: http://tinyurl.com/aae5n6

 

Possibly capsaicin: http://tinyurl.com/csjhqu It is the active ingredient in hot chili peppers and has anti-myeloma activity (see my page on capsaicin)

 

Ginger extract: http://tinyurl.com/cqv9f7 (also anti-myeloma, see my ginger page)

 

Ursolic acid: http://tinyurl.com/bn86pr  Found mainly in: rosemary, apples, bilberries, cranberries, pears, peppermint, lavender, oregano, holy basil, thyme and prunes (see my page on the anti-myeloma effects of ursolic acid, which inhibits STAT3).

 

Olive oil: http://tinyurl.com/begrvy

 

Blueberries: http://tinyurl.com/bm3zsz  

 

White wine (compounds): http://tinyurl.com/dby9jf

 

Xanthohumol: http://tinyurl.com/dc8kvg Found in beer.

 

Caffeic acid: http://tinyurl.com/b64y2s Found in many fruits, vegetables and herbs. Also in, drum roll!, coffee!

 

Grapes and grape extract: http://tinyurl.com/bzk7rh

 

Anything from the Brassicaceae family (= broccoli, cabbage…): http://tinyurl.com/aw2f8h

 

And finally, we should eat truckloads of artichokes, which contain silymarin, an active compound in milk thistle and IL-1 beta inhibitor: http://tinyurl.com/bpyzqj  

 

More to come…

 

Update February 27 2009: Eat pomegranates! A dear friend (grazie!) sent me a study on pomegranates yesterday morning. In the bibliography, I found a 2005 study (abstract: http://tinyurl.com/dh685b; the full study is free, too) discussing a substance called PFE, or pomegranate fruit extract. The exciting bit is that PFE inhibits IL-1 beta, which, as you may recall, is a key player in the progression from smouldering or inactive myeloma to active myeloma. Hah! (My February 1st and 5th 2009 posts deal with IL-1 beta and its inhibitors.)

 

Since the full PFE study is available online, I won’t bother going into too many details. Just a few notes.

 

Let’s start with a sentence in the abstract: Interleukin (IL)-1beta induces the expression of matrix metalloproteinases (MMPs) implicated in cartilage resorption and joint degradation in osteoarthritis (OA). Okay, so this study doesn’t specifically mention multiple myeloma, but it is still relevant to us. You see, MMPs are enzymes that play a role in bone destruction and neoplastic growth (they contribute to angiogenesis, e.g.). I read that our myeloma cells actually produce MMPs in order to hollow out our bones…at any rate, simply put, MMPs are evil, evil thingies, and anything that inhibits them is good. As is anything that inhibits IL-1 beta.

 

Well, this pomegranate extract fits the bill. It inhibits the expression of IL-1 beta-induced MMPs.

UPDATE. March 16 2009 post. Occasionally I come across more substances that inhibit, or may inhibit!, IL-1 beta, which is a key SMM-MM progression factor (see my page on IL-1 beta or my early February posts). Just the other day I found another one: oats! Or, more precisely, polyphenols from oats called avenanthramides. A 2008 study on the prevention of atherosclerosis (see: http://tinyurl.com/croz5k) tested human aortic endothelial cells with the purpose of determining if the mechanism of inhibitory effect of these polyphenols from oats on the expression of proinflammatory cytokines is mediated through modulation of nuclear factor-kB-dependent transcription.

 

This study (grazie, Sherlock!) mainly examines a synthetic form of avenanthramides called CH3-Avn-c, which, to be honest, is of little interest to me (ALL I need is another pill or capsule, argh!). I am more interested in the following:

 

Taken together, our results demonstrate that Avns, specific polyphenols from oats, possess potential anti-inflammatory properties, which may lend to their potential beneficial effect in the prevention of atherosclerosis through inhibition of NF-kB activation. It is interesting to note that oatmeal bath has been used for skin conditions such as eczema, poison ivy, insect bites, sunburn, and shingles, where inflammation is known to be the main culprit. Our findings are in line with the observation of several naturally occurring polyphenols in foods, spices, and herbs, such as curcumin, myricetin, quercetin, resveratrol, and green tea constituent (–)-epigallocatechin-3-gallate (EGCG), all of which have been suggested to have health benefit effects through long-term consumption by modulating NF-kB activity.

 

Long-term. Hmmm. This adjective is a good reminder that there are no quick fixes with natural extracts. Patience is key. If something doesn’t work immediately, perhaps we shouldn’t discard it right off the bat. Well, unless our markers worsen, of course. That’s a different story…

 

Another important excerpt: Our data also point to the potential benefit of including oats and oat bran in daily meals over the long term. Oat products not only are known to reduce blood cholesterol, but also may help to suppress the inflammatory process associated with the development of atherosclerosis. “Long term” is mentioned again in this paragraph. Eh. We are also reminded that oats have a beneficial effect on blood pressure and are a rich source of many nutrients and antioxidants including vitamin E, phytic acid, and unique polyphenols, avenanthramides.

 

Well, including oats in our diet may not do much to inhibit IL-1 beta in the short term (no quick fixes!), but they are good for us in so many other ways. I am going to eat more (organic) oats from now on. In fact, I just had a bowl of (organic) oatmeal and flaxseed for lunch!

 

My motto of the week: can’t hurt…could help!

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