IL-1beta involved in progression from inactive to active myeloma

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: on a Mayo Clinic study titled “Targeting the Pathogenic Role of Interleukin 1beta in the Progression of Smoldering/Indolent Myeloma to Active Disease,” (abstract:; full study: 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.: and 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) and

2.     omega-3

3.     genistein

4.     EGCG

5.     resveratrol

6.     ellagic acid (on my to-be-tested list)


I will stop here because I want to go give my husband a big bear hug…and do another little jig of joy around the room on the way! Yippity yippity doodle! Evvaiiiii, grandeeeee!!! 🙂


  1. are just too darn cute!!! You not only share wonderful news with us but you do it in such a way that we feel that we are there with you…celebrating the moment…doing a jig! I’m off the Nature’s Cupboard to pick up MORE supplements! : )

  2. This is a great post-Thank you! I gave the links and info on to our Forum in Germany and I am sure that it will be very much appreciated!

  3. I ordered a boat load of curcumin, but have been terrible at remembering to take it. I wonder if there’s be any problem with taking at bed time each night so I can develop the habit? Do you take all your stuff at once?

  4. Thanks, everyone. Well, I might have missed this Mayo study had it not been for two good list friends, so you can imagine that I am very grateful to them both (as I wrote on the myeloma list this morning, I wish I could give them both a big hug!), as I am to all the readers who send me stuff. Keep on sending…and I will try to read everything!

    Beth, it’s a fact that the immune system is stronger at night (this anticipates one of my upcoming posts, still in early draft form), so why not take curcumin before going to bed? Go ahead and give it a try. I take all my supplements right before dinner.


  5. Well I think you certainly should jump for joy, I think you are doing a fantastic job of pulling together such a lot of information which hopefully will help us all.

    Whilst looking for something else this morning I found this summing up report on curcum written in 2008 I thought you may be interested

    the thing I was looking up was curcumin’s ability to effect topoisomerase as I couldn’t remember and of course yes it inhibits it, the reason? I have been recently reassessing why I take some of my herbs and had just read that research had shown that Lapacho’s (Pau d’Arco; Taheebo) anti cancer ability was due to inhibiting topoisomerase, “Based on its traditional uses, lapacho is sometimes recommended by herbalists as a treatment for cancer. However, there is no reliable scientific evidence that the herb is effective. Test tube studies have found that lapachone can kill cancer cells by inhibiting an enzyme called topoisomerase, and there are hopes that effective anti-cancer drugs may eventually be produced through chemical modification of lapachone.4-11 Nonetheless, this does not indicate that lapacho is effective against cancer in humans”. So I radomly decided to check if Curcumin did as well.

    Here is a study showing Lapacho’s positive effect against drug resistant MM cell lines. .. So that herb is definately staying, although bioavailabilty is a issue.

    Love and health


  6. Hey Sue, guess what? Months ago I wrote a draft about beta-lapachone and MM, citing this particular study and another one, too. What a coincidence, huh? I haven’t yet gotten around to publishing my draft because beta lapachone is a highly toxic plant extract (AND poorly bioavailable, to boot). Whenever I read the words “highly toxic,” you see, I lose interest. Therefore, as long as I have more interesting substances to write about, my post on beta lapachone will remain an unpublished draft.

    I’d seen the Lin article even though some time ago I had to get delete my Google Alert for “curcumin” because I was receiving too much stuff on a daily basis. I just didn’t/don’t have the time to read it all. So if you come across things like this, please let me know. I might miss ’em!


  7. Hi Margaret,

    Here is a pubmed abstract that discusses the benefits of taking three very common, relatively cheap and very safe supplements at low doses that may not only reduce levels of il-1b, but also il-6, il-8 as well as tnf-alpha and vegf! Not a bad group to keep under control for many medical conditions at a price that’s hard to beat. Good safety profile on all three also.

    1: Basic Clin Pharmacol Toxicol. 2007 Jun;100(6):387-91. Links
    Serum cytokine levels of interleukin-1beta, -6, -8, tumour necrosis factor-alpha and vascular endothelial growth factor in breast cancer patients treated with tamoxifen and supplemented with co-enzyme Q(10), riboflavin and niacin.Premkumar VG, Yuvaraj S, Vijayasarathy K, Gangadaran SG, Sachdanandam P.
    Department of Medical Biochemistry, Dr ALMP-GIBMS, University of Madras, Taramani Campus, Tamilnadu, India.

    The prognostic significance of supplementing co-enzyme Q(10) (CoQ(10)), riboflavin and niacin (CoRN) along with tamoxifen to breast cancer patients was evaluated by measuring the serum cytokine levels of interleukin (IL)-1beta, IL-6, IL-8, tumour necrosis factor alpha (TNF-alpha) and vascular endothelial growth factor. In the present study, 84 breast cancer patients were randomized to receive a daily supplement of CoQ(10) 100 mg, riboflavin 10 mg and niacin 50 mg, one dosage per day along with tamoxifen 10 mg twice a day. Serum cytokine levels were elevated in untreated breast cancer patients (Group II) and significantly reduced after tamoxifen therapy for more than 1 year (Group III). When group III breast cancer patients were supplemented with CoRN for 45 days (Group IV) and 90 days (Group V) along with tamoxifen, a significant reduction in cytokine levels were observed (P < 0.05). Such a decrease in serum cytokine levels after CoRN supplementation in breast cancer patients may suggest good prognosis and efficacy of the treatment, and might even offer protection from metastases and recurrence of cancer.

  8. Hi again Margaret.

    Slightly off topic, but possibly relevant.

    Here is a pubmed abstract which discusses the effect that il-1b has on il-23…….a known problem area in relation to Celiac Disease.

    1: J Immunol. 2008 Oct 1;181(7):4457-60. Links
    Cutting edge: IL-1 controls the IL-23 response induced by gliadin, the etiologic agent in celiac disease.Harris KM, Fasano A, Mann DL.
    Pathology Department, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

    IL-23 has been implicated in the pathogenesis of several tissue-specific autoimmune diseases. Currently, celiac disease (CD) is the only autoimmune disease in which both the major genetic (95% HLA-DQ2(+)) and etiologic factors (dietary glutens) for susceptibility are known. We demonstrate that wheat gliadin induces significantly greater production of IL-23, IL-1beta, and TNF-alpha in PBMC from CD patients compared with HLA-DQ2(+) healthy controls, strongly advocating a role for IL-23 in the pathogenesis of CD. Moreover, IL-1beta alone triggered IL-23 secretion and the IL-1R antagonist inhibited this response in PBMC and purified monocytes. This sequence of events was replicated by beta-glucan, another substance known to induce IL-23 production. Our results suggest that gliadin and beta-glucan stimulate IL-23 secretion through induction of the IL-1 signaling pathway and reveal for the first time that the IL-1 system regulates IL-23 production. These findings may provide therapeutic targets for this disease and other inflammatory conditions mediated by IL-23.

    PMID: 18802048 [PubMed – indexed for MEDLINE]

  9. Hi Margaret.

    Here is a pubmed abstract showing that Silymarin from milk thistle can have a negative impact on il-1b. Other studies have shown that it can also act as an antioxidant, anti inflammatory and can be anticarcinogenic with a fairly good safety profile, and in the Syliphos form, can have improved bioavailability.

    1: Biochem Pharmacol. 2004 Jan 1;67(1):175-81. Links
    Protection against lipopolysaccharide-induced sepsis and inhibition of interleukin-1beta and prostaglandin E2 synthesis by silymarin.Kang JS, Jeon YJ, Park SK, Yang KH, Kim HM.
    Korea Research Institute of Bioscience and Biotechnology, Taejon, South Korea.

    Silymarin is known to have hepatoprotective and anticarcinogenic effects. Recently, anti-inflammatory effect of silymarin is attracting an increasing attention, but the mechanism of this effect is not fully understood. Here, we report that silymarin protected mice against lipopolysaccharide (LPS)-induced sepsis. In this model of sepsis, silymarin improved the rate of survival of LPS-treated mice from 6 to 38%. To further investigate the mechanism responsible for anti-septic effect of silymarin, we examined the inhibitory effect of silymarin on interleukin-1beta (IL-1beta) and prostaglandin E2 (PGE2) production in macrophages. Silymarin dose-dependently suppressed the LPS-induced production of IL-1beta and PGE2 in isolated mouse peritoneal macrophages and RAW 264.7 cells. Consistent with these results, the mRNA expression of IL-1beta and cyclooxygenase-2 was also completely blocked by silymarin in LPS-stimulated RAW 264.7 cells. Moreover, the LPS-induced DNA binding activity of nuclear factor-kappaB/Rel was also inhibited by silymarin in RAW 264.7 cells. Taken together, these results demonstrate that silymarin has a protective effect against endotoxin-induced sepsis, and suggest that this is mediated, at least in part, by the inhibitory effect of silymarin on the production of IL-1beta and PGE2.

    PMID: 14667940 [PubMed – indexed for MEDLINE

  10. Hi Margaret,
    In one of the em’s I sent you, I said that I thought ashwagandha was not an il-1b inhibitor, but it does seem to inhibit it as well as il-6.
    Here is a pubmed abstract that discusses that point.

    1: Evid Based Complement Alternat Med. 2008 Jan 10. [Epub ahead of print] Links
    Genomic Analysis Highlights the Role of the JAK-STAT Signaling in the Anti-proliferative Effects of Dietary Flavonoid ‘Ashwagandha’ in Prostate Cancer Cells.Aalinkeel R, Hu Z, Nair BB, Sykes DE, Reynolds JL, Mahajan SD, Schwartz SA.
    Pediatrics, and Microbiology, Chief, Division of Allergy, Immunology & Rheumatology State Universtiy of New York at Buffalo, Interim Chief, Department of Medicine, Kaleida Health – Buffalo General Hospital 100 High Street, Buffalo, NY 14203, USA.

    Phytochemicals are dietary phytoestrogens that may play a role in prostate cancer prevention. Forty percent of Americans use complementary and alternative medicines (CAM) for disease prevention and therapy. Ashwagandha (Withania somnifera) contains flavonoids and active ingredients like alkaloids and steroidal lactones which are called ‘Withanolides’. We hypothesize that the immunomodulatory and anti-inflammatory properties of Ashwagandha might contribute to its overall effectiveness as an anti-carcinogenic agent. The goal of our study was gain insight into the general biological and molecular functions and immunomodulatory processes that are altered as a result of Ashwagandha treatment in prostate cancer cells, and to identify the key signaling mechanisms that are involved in the regulation of these physiological effects using genomic microarray analysis in conjunction with quantitative real-time PCR and western blot analysis. Ashwagandha treatment significantly downregulated the gene and protein expression of proinflammatory cytokines IL-6, IL-1beta, chemokine IL-8, Hsp70 and STAT-2, while a reciprocal upregulation was observed in gene and protein expression of p38 MAPK, PI3K, caspase 6, Cyclin D and c-myc. Furthermore, Ashwagandha treatment significantly modulated the JAK-STAT pathway which regulates both the apoptosis process as well as the MAP kinase signaling. These studies outline several functionally important classes of genes, which are associated with immune response, signal transduction, cell signaling, transcriptional regulation, apoptosis and cell cycle regulation and provide insight into the molecular signaling mechanisms that are modulated by Ashwagandha, thereby highlighting the use of this bioflavanoid as effective chemopreventive agent relevant to prostate cancer progression.

    PMID: 18955307 [PubMed – as supplied by publisher]

  11. Margaret, that is excellent news. It really helps to pull threads together.

    Art, Thanks for posting that note on gluten. I am currently resigning myself to the necessity of going permanently gluten free (it clearly affects me but it’s hard work being gluten and dairy free). This pretty much clinches the deal. I have seen figures suggesting the true rates of gluten sensitivity are as high as 1 in 35 people. Makes me wonder if the high levels of gluten consumption in western society are responsible for our high levels of immune dysfunction and cancer.


  12. I’ll second what Lyn says. I agree that high gluten consumption in our society causes a lot of problems – not least of which is obesity. The excess intake of omega 3 is also likely to be pro-inflammatory.
    I am also grateful to both Margaret and Art for their posts.
    I’ve been on a gluten free diet for 18 months now and there has been a gradual impovement in my general health. My paraprotein has also remained flat for the last 4 years.
    Best wishes to all,

  13. Art, I hadn’t yet read your comments (just did)…evidently we are on the same wavelength. And guess what? Ashwagandha has anti-myeloma effects. It is on my to-be-researched list.

    But first, I have to write about another substance (lips are sealed) 🙂 …interesting times, these!

  14. Well, I don’t have a prostate gland, so I am sure that I don’t have to worry about any silly prostateglandins… 😉

    Okay, seriously now. I read that abstract. Good one. Convincing. And actually, I have been eating less pasta recently. I am also expanding my cooking repertoire a wee bit. For instance, I just learned how to make my own homemade chili (wow, goooood stuff!) with tons of hot red pepper, turmeric and other spices. Garlic, too. It really helps that Stefano doesn’t like pasta that much AND likes to try new things.

    I may give up pasta entirely some day, but boy, that will be a toughie. You know that question “if you were on a desert island and could have only one type of food every day for the rest of your life, what would it be?”? Well, I have always answered pasta with tomato sauce. Today, though, I might answer: a vegetarian curry dish with lots of turmeric…

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