The pain lozenge

Curcumin effectively inhibits NF-kappaB only in combination with IL-10

Natural NF-kB inhibitor acts in a synergistic manner to stop inflammation in IBD.

This is an important publication because it:

  • Demonstrates one likely reason you can’t overdose on curcumin or any other natural NF-kB inhibitor;
  • Suggests ‘cooperation’ between these natural NF-kB inhibitors and the immune system – a ‘vitamin like’ action; and,
  • Provides one example of the importance of natural NF-kB inhibitors in shutting down inflammation.

Each of the above is consistent with the theory of inflammation advanced on this site.

Curcumin & IL-10

Curcumin (a major active component of turmeric) has been shown to exert substantial anti-inflammatory effects. Many studies suggest that it acts primarily by inhibiting NF-kB.

IL-10 is an important chemical messenger in the immune system and a regulator of inflammation. Like most such immune regulating molecules, it interacts with many other components of the immune system in a complex manner resulting in diverse effects. However, IL-10 acts primarily to inhibit/reduce inflammation, largely by inhibiting NF-kB.

IL-10 is especially important in the digestive tract and may play a role in the onset and progression of inflammatory bowel disease: Crohn’s and ulcerative colitis patients may suffer from a deficiency of IL-10.

NF-kB & inflammatory bowel disease

Inflammatory bowel disease is strongly associated with excess activation of NF-kB.

Ulcerative colitis patients and, to a lesser extent Crohn’s patients, have been found to benefit from administration of curcumin – presumably because of its ability to inhibit NF-kB.

Drugs frequently used as first-line therapy for inflammatory bowel disease, such as glucocorticoids or aminosalicylates (e.g. sulfasalazine) are also inhibitors of NF-kB.

NF-kB inhibition, at least in the treatment of inflammatory bowel disease, seems to be a good thing.

IL-10 & curcumin – synergy & dependence

The study briefly summarized below demonstrates a synergistic effect between IL-10 and curcumin. In other words, IL-10 was much more effective as an NF-kB inhibitor when curcumin was present.

That’s significant because a difficulty in shutting down inflammation is common to many of the inflammation related conditions. Much of autoimmune disease is, I believe, not so much a primary attack on the body by one’s own immune system as it is an immune system that can’t turn inflammation off, and so ends up attacking all sorts of things (organs, joints, skin, nerves, etc.)

Also, curcumin was unable to inhibit NF-kB when IL-10 was absent.

The latter fact is quite surprising. Curcumin is ‘supposed’ to inhibit NF-kB – but in this study it stopped doing so when IL-10 was absent.

So it seems that when your body is trying to shut down inflammation – when IL-10 is present – curcumin comes alongside and joins in the battle. Then, once that excess inflammation is relieved (IL-10 no longer present) curcumin simply stops acting.

Something unexpected is going on. Curcumin seems as if it is ‘cooperating’ with the immune system, or perhaps being actively and selectively used by the immune system as a ‘tool’ of assistance in shutting down inflammation. To some  extent, curcumin seems to be acting like a vitamin.

When the body requires a vitamin it grabs one from the circulation. When that same vitamin is not needed it simply washes away (the water soluble vitamins at least.) But the vitamin has to have been taken in (eaten.) If not – if there is no vitamin to grab – then a deficiency disease will soon develop. The body cannot function properly without the vitamin.

Perhaps the body requires some minimum level of these natural NF-kB inhibitors in order to function properly. Perhaps a shortage of natural NF-kB inhibitors results in a deficiency disease that we recognize as various forms of inflammation. No, I don’t think we need curcumin per se, but I do think we need a steady supply of natural NF-kB inhibitors. I think we need this ‘class’ of molecule – call it a “vita-class.”

We know very little of what really goes on

While it’s fair to note the above description of curcumin and IL-10 (or everything on this site) as a gross oversimplification – I think it’s also fair to say that everything written on the immune system is grossly simplified – because we still know so very little of what really goes on ‘in there.’

No one could have guessed that curcumin would be found powerless in the absence of IL-10. And tomorrow something new will be discovered, and the day after, and the day after….

Curcumin just happens to be one of the better studied molecules – so at least we know a little. But curcumin certainly isn’t the only molecule that will be found to act in surprising ways. The interaction of curcumin and IL-10 is no doubt only one of a great many yet undiscovered examples of such synergistic cooperation.

The publication:

November, 2008

Limited effects of dietary curcumin on Th-1 driven colitis in IL-10 deficient mice suggest an IL-10-dependent mechanism of protection.

Summary of the abstract (or you can read the free full-text publication online)

Curcumin (a major active ingredient in turmeric) demonstrates profound anti-inflammatory effects in intestinal epithelial cells (IEC) and in immune cells in vitro (“vitro” refers to glass – so in vitro refers to experiments in a ‘test tube’ – outside of a living organism.)

Curcumin also exhibits a protective role in rodent models of chemically induced colitis, with its presumed primary mechanism of action via inhibition of NF-kappaB.

Although it has been demonstrated effective in reducing relapse rate in ulcerative colitis patients, curcumin’s effectiveness in Crohn’s disease (CD) has not been evaluated.

Therefore, the effects of dietary curcumin were investigated in respect to the development of colitis, immune activation, and NF-kB activity in a mouse model of colitis.

Curcumin showed a mild protective effect on the colon.

Surprisingly, activation of NF-kB in mice without IL-10 was not noticeably inhibited by curcumin.

Furthermore, it was demonstrated that IL-10 and curcumin act in a synergistic manner to inhibit NF-kB activity.  This study in the mouse model suggests that the protective effects of curcumin are IL-10 dependent.


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