Curcumin Restores T Cells

Doing research for a recent post, as frequently happens, I came across an interesting abstract with some hard-to-believe news. My brilliant friend Sherlock (grazie!) kindly sent me the full study, published in the Journal of Biological Chemistry in June 2007. According to the abstract (http://tinyurl.com/3yqzc6), Administration of curcumin to tumor-bearing animals resulted in restoration of progenitor, effecter, and circulating T cells. Curcumin can reinstate our T cells at every stage of their development? No way! (Yes, way). Hmmm, the question arises: why should we care about T cells? Well, if we didn’t have any T cells, we would be like nude mice, yes, the sort used in lab experiments. We would have no way of fighting off disease. T cells, in a nutshell, are crucial players in our immune response to diseased cells.

Let’s take a look at the full study: In order to establish itself, a growing tumor must evade the immune system of the host. This contributes to tumor-induced immune suppression. A growing tumor can evade the proposed immune surveillance by several mechanisms. One of these mechanisms is to kill (induce apoptosis of!) our T cells. Reading on, we learn that Increased oxidative stress because of the growing tumor can be another cause of immune disruptions. Recently, several observations indicate that a chronic inflammatory condition develops in patients with advanced cancer, causing oxidative stress that can shut off immune functions, including those of T and NK cells. Oh, this is not good at all.

Before proceeding, let me just mention that I was confused enough about all these different types of cells that today I looked everything up, from A to Z. I am now in the midst of putting together a brief (!) explanation (?) of a very complex topic. For now, let it suffice that B, T and NK (natural killer) cells are three types of lymphocytes (white blood cells) that originate from hematopoietic stem cells (HSCs), located in the bone marrow. They have different functions, but we don’t need to get into the nitty gritty, yet. If you can’t wait for my explanation, then click on the fabulous link I provide below. Back to the study, now.

A tumour has a negative influence on the production of T cells in the thymus, which is a small organ, located behind the sternum, that produces T cells (the “T” stands for “thymus,” in fact). A tumour causes a massive depletion of both thymic and circulatory T cell populations. Massive depletion of T cells? Yikes. But there is GOOD news. The administration of curcumin brought back thymic CD4+8+, CD4+, and CD8+ cells as well as circulatory effecter CD4+ and CD8+ cells to control level. (CD4 and CD8 are the two main T cell subsets, by the way.) Curcumin brought these cells back to CONTROL level? Well, knock me down with a feather!

Ah, but it gets better. Curcumin protected T cells from being killed by the tumour. When preincubated with curcumin, these cells turned into Superduperfantastic cells, resistant to any tumour attack (sort of like Harry Potter versus Voldemort). In other words, they survived. Oh, sure, this is all happening in vitro. But the researchers experimented with mice, i.e., in vivo, too. Exact same results. They conclude that from aforementioned in vitro and in vivo results, it may be envisaged that curcumin might also protect T cells from a tumor-induced demise in humans. Hey, it’s not every day that I get excited about something called thymic CD4 plus! ūüėČ

My next topic stumped me for hours, it seems, until I came across an absolutely brilliant website that opened up a whole new world for me: the world of relatively easy biology. Itsy bitsy thingies no longer have any secrets for me thanks to John Kimball, a retired biology professor who taught at Tufts and Harvard (I must remember to write him a glowing fan letter). The updated sixth edition of his biology textbook is online (free, too): http://tinyurl.com/57ygj So from now on, if you ever have a doubt about, say, the JAK-STAT pathway, this is the place to go. ūüėČ Seriously, though, thank you from the bottom of my heart, Prof. Kimball! Everything is crystal clear now. Well…more or less!

Here’s what stumped me: in the curcumin T cell study, I read that tumours downregulate the anti-apoptotic Bcl-2 protein (take my word for it, this is NOT a good thing). But that’s precisely what curcumin does: it downregulates Bcl-2 in myeloma cells. Wait, how could this be? Why is the downregulation of Bcl-2 bad for T cells, good for myeloma cells? Ah, you see, perhaps, had I written out the question, I wouldn’t have spent hours trying to figure it out!

It’s very simple, really. In the case of T cells, in fact, we WANT to have a high level of Bcl-2. In the case of myeloma cells, we don’t. Prof. Kimball’s page on Bcl-2 explains that B cells, like all activated lymphocytes, die a few days after they have had a chance to do their job. This ensures that they do not linger around after the threat has been dealt with and turn their attack against self components. Aging B cells kill themselves by apoptosis. But high levels of the Bcl-2 protein protect the cells from early death by apoptosis. After reading these four sentences, a light went on in my brain: we want T cells to LIVE, but myeloma cells to DIE. Therein lies the difference. Okay, so it took me hours, not minutes, to figure this out, but I am not a biologist, and I didn’t have this wonderful reference text at my fingertips until the latter part of the afternoon.

Well, we have yet another (!) good reason to take curcumin. I can feel my T cells getting more powerful by the second…!

My brain is fried, now, and I need to get off the computer, but will certainly take a second look at this study at some point over the weekend. I would like to end by pointing out that Mary has some good advice for us (see her most recent comment to my December 3rd post). Please go have a look!

9 Comments

  1. Margaret,

    Your research really amazes me, many biological and physical scientists (most physicians are pratitioners) should be as thorough as you!! Your discussion about T cells brings to mind a test that I have done every 3 months. It is called Immuno-know (Cylex). It measures the activation of T cells. As you may recall, I had a kidney transplant in 2005 and UPMC in Pittsburgh uses this test to monitor immune cell function and to make adjustments to immunosuppression. A terrible side effect to the use of immunosuppressants is lymphoma (and sometimes myeloma). I wonder if this test would be a good way to monitor how various treatments were helping or hurting myeloma patients.

    Chuck Zubritsky

  2. Hi Margaret

    I was going to ask the same question as George, I have also seen the original study on epic4health.com. I think life extensions used better controls to varify the enhanced bioavailablity though. I sounds similar to the Biocurcumax you have highlighted under your heading of curcumin analogues and nanocurcumin. It makes perfect sense really, if you talk to any old school herbalists, they will tell you to take the whole herb, not just part of it as it. As chuck is, I am in awe of your ability to read and then document, the snippets you find. I have been following studies on various herbs, for the last 3 years, my gut feeling told they were going to be helpful. but I seem to get stumped at finding the relevant studies or the medical jargon gets the better of me. I had become a bit disillusioned with looking, but finding your site has given me a new incentive to carry on.
    Wishing you good health

    Sue Hepburn

  3. cara margaret,
    ho da poco saputo degli effetti positivi della curcumina nel trattamento del mieloma, dal tuo blog vedo che stai portando avanti un trattamento; mi interesserebbe sapere di pi√Ļ a questo proposito; soprattutto la curcumina dove si acquista? e in che forma? io ho cominciato a preparare pseudotisane di curcuma, √® la stessa cosa?
    ti ringrazio per il tuo utile blog.
    un bacio L.

  4. Hello Margaret,

    I have been reading about curcumin, as well as your blog, for only a couple of days. There is quite a lot helpful information. However, since the time that I started to search the publications on curcumin in the medical literature, I found it quite controversial in many senses. There is a great deal of research that has been made last year, and for sure, I was not able to examine them all. But I found a paper just published (March 23, 2010) in CCR quite useful, since it is making a general review of the latest debate by citing key studies. Here it is (sorry for the inelegant citation):

    Vermorken, Alphons J.M., Jingjing Zhu Willem J.M. Van de Ven. 2010. “Is Curcumin for Monoclonal Gammopathy of Undetermined Significance without Risk?. Letter in CCR, first published online on March 23, 2010.

    This study warns us about some has-to-be-explored dangers of curcumin for the MGUS patients. It cites several other studies indicating the immunosuppressant role of curcumin since it “prevents human DCs from responding to immunostimulants” (abstract). It continues as:

    “Curcumin seems to dampen the Th1 response. An anti-inflammatory and immunosuppressant role for curcumin was suggested (3). A Th1 pattern of cytokine secretion, in which DC-derived interleukin-12 (IL-12) plays an essential role, is associated with antitumor responses. Dampening of the Th1 response could therefore be counterproductive in attempts to prevent malignant progression in patients in which DC maturation is compromised like in patients with common variable immunodeficiency. Despite heterogeneous clinical presentation, common variable immunodeficiency is generally associated with defective DC functions. DCs appear morphologically normal but lack of IL-12 production and defective antigen presentation shows significant functional defects (4). Whether curcumin inhibits IL-12 production from DCs in MGUS is a crucial question because immunosuppression forms a risk for MGUS progression (5).”

    Another study which cited in this blog under the headline “Curcumin and Immune Disorders” posted on April 7, 2007, interprets the actions of curcumin on T-cells as immunoregulatory. (Well, as far as I understood. The paper is very tricky for a non-professional who has been reading medical literature for the last few days. I will try it tonight again.)

    The immunosuppressive–or immunoregulatory–effects of curcumin requires a broader research. In line with this, I find it very useful for you to bring this debate to your blog under a separate entry to update people about the controversies of curcumin in the literature, and its developments (maybe you have one, but I could not find). So far, as far as I understand, this is the most serious possible negative side of curcumin on MGUS patients. You have been discussing curcumin in your blog in a great deal, and this is great. But I think, these studies deserve to be discussed more for further investigations of the patients, such as if it is making a negative immunosuppressive effect, then what shall we do to reverse it; should we adjust the dose, take it with a supplement, etc.

  5. Yes, curcumin as well as many other anti-inflammatory supplements and compounds INCLUDING Omega 3 EPA DHA are IN FACT immunosuppressive. This is the confusion that comes with understanding cancers. This is due to the fact that many cancers thrive on a stimulated immune system that drives inflammation, and others actually need an immune response to destroy them. this is mediated by the inhibition of Nfkb within macrophages and tumor cells.

  6. I would like to add a quick note in response to Dugyu’s well thought remarks:

    I did a quick survey of the literature on Curcumin to ascertain whether it dampens or supports T cells & Dendritic antigen presentation etc.

    All the studies that claim immunosuppression seem to be in-vitro. As I’m sure you are aware of, feeding an animal or human curcumin is far far more complex than a simplistic in-vitro test. Issues of concentration arise. Also the immune system is highly (exasperating complex).

    There is also the other HUGE side of immunotherapy that addresses the highly immunosuppressive tumor microenvironment. For decades, we’ve tried to “stimulate” or “target” the immune system. Now, solid science is being backed up by real drugs that clearly show that we need to address the immunosuppressive microenvironment around tumors (Tregs, Myeloid Derived Suppressors). Those who haven’t already looked at anti-PD1, anti CTLA4, I highly recommend you do so. These drugs are revolutionizing immunotherapy, notably ASCO 2012 results showing 20% responses in NSCLC via anti-PD1 (NSCLC has traditionally failed all “targeted” immunotherapies and thought to be non-immunogenic).

    In summary, I highly recommend careful attention be directed as to whether studies are in-vitro vs in-vivo. That said, there are very few in-vivo studies, but what is out there seems to favor the supportive effect of dietary curcumin on T cells.

    As to whether “supercharged” bio available curcumin may lead to “too high concentrations of curcumin detrimental to Tcells”, that may be able to be calculated if pharmacokinetic data exists for that specific curcumin formulation. Even so, this still does not address the multi-factorial nature of the highly complex immune system.

  7. Margaret,

    I have found your research impeccable! As I have stage 4 triple negative breast cancer, I have been researching as well into natural compounds that impact tumor viabity and metastatic progression. Curcumin hits all the pathways.
    Recently I have been impressed with studies on its impact on immunity as I had concerns on its impact on cytotoxic T cells. Indeed, it improves T cell function by altering the tumor induced immune suppression. It inhibits TGF beta which induces immune dysfunction and which generates epidermal growth factor, the source of multiple tumor oceanic pathways in breast cancer (and many cancers).
    See: “Curcumin Reverses T Cell Mediated Adaptive Immune Dysfunction in tumor – Bearing Hosts” by S. Bharat harts in Cellular and Molecular Immunogy

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