Category Archives: Autoimmune Disease

Autoimmune disorders

Ginger inhibits inflammation – affects macrophages & T-cells

Activated macrophages are present in high concentrations in a number of inflammatory lesions. The most common inflammatory cell identified in active central nervous system lesions of multiple sclerosis is, for example, the macrophage.

The study briefly summarized below may have implications on the possible use of ginger extract in the treatment of multiple sclerosis, especially to the extent that ginger extract was associated with a significant reduction in T cell proliferation in response to allostimulation – thought to be important in the pathology of multiple sclerosis.

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Glucocorticoid therapy in MS inhibits NF-kB

Methylprednisolone administration in multiple sclerosis patients (pulsed therapy) resulted in clinical improvement that showed a correlation to NF-kB inhibition.
The publication:
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J Neurol Sci. 2008 Jan 15;264(1-2):145-50.
Changes in the activation level of NF-kappa B in lymphocytes of MS patients during glucocorticoid pulse therapy.
Eggert M, Goertsches R, Seeck U, Dilk S, Neeck G, Zettl UK.
Department of Internal [...]

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Blessed milk thistle may bless those with MS

Silibinin is a mixture of flavonolignans extracted from blessed milk thistle. It has for some time been recognized for its beneficial effects in protecting the liver against toxins. More recently it has been demonstrated that silibinin inhibits NF-kB.

The researchers whose publication is briefly summarized below hypothesized that, as a natural NF-kB inhibitor, silibinin might be useful in the treatment of multiple sclerosis.

Employing the mouse model of MS, experimental autoimmune encephalomyelitis (EAE), they looked at the effects of silibinin on spinal cord demyelination and inflammation. The results of their investigation indicated that silibinin is both immunosuppressive and immunomodulatory and that it might be useful in the treatment of MS.

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Fumaric acid inhibits NF-kB, treats psoriasis and perhaps MS

Fumaric acid is widely used in Germany (where it is known as Fumaderm®) in the treatment of psoriasis. It’s mechanism of action is uncertain, but it is believed to act primarily via the inhibition of NF-kB through by increasing the levels of reduced glutathione.

A total of 13 studies have confirmed that 50-70% of psoriasis patients show an approximate 75% reduction in their “psoriasis area and servitiy index” (PASI) after 4 months of treatment. However, side effects can be significant, and include nausea, vomiting and diarrhea in up to 30% of patients. These side effects limit the duration of treatment to 6 weeks, which of course limits the usefulness of this product in the treatment of chronic disease.

Fumarate is known to be an immunomodulator, which is one reason for its present consideration as a possible new drug for the treatment of multiple sclerosis.

In a recent phase II study involving 257 patients, fumarate reduced by 69% the average number of lesions on MRI between weeks 12 and 24, reduced newly enlarging lesions by about 50% and reduced the annualized relapse rate by 32%. Adverse events included headache, infections, GI symptoms and slightly increased liver enzymes, all of which were reversible.

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Natural inhibitor of NF-kB as potential new treatment for multiple sclerosis

Triptolide, the presumed active component of T. wilfordii, is known to be an inhibitor of NF-kB.In the study briefly summarized below, oral administration of triptolide was shown to be therapeutic in a mouse model of multiple sclerosis, both when used as an acute treatment (after development of disease) and when used in the prevention of disease onset.

Experimental autoimmune encephalomyelitis (EAE) is a well accepted animal model of human demyelinating disease such as multiple sclerosis. However, it should be noted that the condition studied is not multiple sclerosis, and that the ‘patient’ is a mouse, not a human.

Nonetheless, the results of oral administration of the natural NF-kB inhibitor triptolide were encouraging:

* Disease onset was delayed.
* Clinical symptoms were reduced.
* Relapse rate decreased.
* Inflammation and demyelination in CNS tissue were both diminished.

Triptolide was shown to inhibit NF-kB.

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Progressive MS might be effectively treated via NF-kB inhibition.

Inhibition of NF-kB was found to be effective in preventing relapse in a mouse model of multiple sclerosis.
The publication:
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J Autoimmun. 2000 May;14(3):205-11.
Treatment of established relapsing experimental autoimmune encephalomyelitis with the proteasome inhibitor PS-519.
Vanderlugt CL, Rahbe SM, Elliott PJ, Dal Canto MC, Miller SD.
Departments of Microbiology-Immunology, 38 Sidney Street, Cambridge, MA 02139, USA.
Summary of the [...]

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Pregnancy lowers relapse in MS via NF-kB inhibition

Lower relapse rates in multiple sclerosis patients during pregnancy result from higher levels of estrogen leading to NF-kB inhibition.

Women with multiple sclerosis have been reported to suffer fewer relapses (attacks or disease exacerbations) during the time of pregnancy. While there has been some controversy on this issue, the PRIMS study (pregnancy and MS study) documented a modest but significant decrease in the rate of relapse in 227 women with MS during pregnancy, especially during the third trimester. Those same women then experienced a higher than normal (pre-pregnancy) rate of relapse following childbirth, especially in the first three months after childbirth.

Increased estrogen (or estriol) levels during pregnancy have been postulated as the source of this ‘protective effect’.

In the study summarized below, the researchers note the effects of estriol on various mediators of inflammation and on the inhibition of NF-kB.

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Genetic study points to NF-kB dysregulation in MS

Variation in genes controlling inhibitors of NF-kB strongly influences susceptibility to multiple sclerosis.

Multiple sclerosis (MS) is known to be associated with both excess, chronic inflammation and with immune dysfunction. Since NF-kB is central to the control of inflammation, the researchers whose publication is summarized below investigated genetic variations associated with NF-kB in multiple sclerosis patients.

That is, rather than looking at the entire genome (all the genes in an individual) they only investigated those genes related to NF-kB. By focusing on and more closely examining NF-kB, more subtle differences can be investigated, especially the combination of slight differences between individuals with and without MS. Specifically, they looked for mutations, polymorphisms and sequence variations (MPSV) in NF-kB related genes.

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Parthenolide for migraine and MS

Parthenolide, though previously shown to inhibit NF-kB, was shown in the study summarized below to inhibit NO production through an alternate pathway. It is likely that parthenolide (the presumptive active component of feverfew) acts by various mechanisms in the body.

The investigators conclude that parthenolide might be useful in the treatment of those conditions where excess NO is believed to play a significant role, such as multiple sclerosis and migraine.

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The weak NF-kB inhibitor glucosamine may be useful in IBD.

Essentially all NF-kB inhibitors, even the relatively ineffective NF-kB inhibitor glucosamine, may be of benefit in the treatment of diverse conditions associated with inflammation – including inflammatory bowel disease.

Glucosamine, which was originally combined with chondroitin sulfate in preparations for the treatment of osteoarthritis, was originally believed to act primarily by “re-building cartilage” and “providing nutrition” to the joint.

It is now recognized, however, that glucosamine is an anti-inflammatory agent – a weak NF-kB inhibitor.

As such, glucosamine will do what NF-kB inhibitors do – it will treat inflammation and may therefore find application in any number of inflammation related conditions.

In the study summarized here, the effects of glucosamine in the treatment of a rat model of inflammatory bowel disease are investigated and found to be promising.

However, it is this author’s opinion that glucosamine will never find practical application in the treatment of inflammatory bowel disease (ulcerative colitis and Crohn’s.) It is simply not a potent enough inhibitor of NF-kB and would require administration in amounts far too great to be practical.

Furthermore, there are much more effective, faster-acting NF-kB inhibitors readily available.

Nonetheless, this study serves as a useful demonstration of the safety and efficacy of NF-kB inhibitors – in this case when used for the treatment of inflammatory bowel disease.

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Natural NF-kB inhibitor acts synergistically to stop inflammation in IBD

Curcumin effectively inhibits NF-kB only in combination with IL-10.

This is a key 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.

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HTLV-1 associated with Sjogren’s

When NF-kB is excessively stimulated, cells cannot die normally (this normal cell death is called “apoptosis.”) This study suggests that HTLV-1 results in the activation of NF-kB (so normal cell death does not occur.) This then results in an increase of cytokine production (inflammation) and cell proliferation, which is thought to be one cause of autoimmune disorders such as Sjögren’s syndrome and rheumatoid arthritis.

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Demyelination: a vicious cycle in multiple sclerosis

Multiple sclerosis (MS) is generally regarded as an autoimmune disease – one in which the immune system mistakenly attacks a part of the body – in this case the covering of neurons in the central nervous system.

Without their insulating cover, the nerves do not function properly. MS can result in widely varying symptoms depending on which nerves are ‘attacked.’

The study abstract summarized below does not directly reference multiple sclerosis. But it does suggest one possible mechanism by which an initially small lesion could progress, and how the disease might be self-sustaining.

Damage to the nerve covering – the myelin sheath – releases sulfatide. Sulfatide then triggers inflammation via activation of NF-kB. The inflammation leads to further damage to the nerve sheath, further release of sulfatide, more NF-kB activation, more inflammation, etc.

It seems likely that those without multiple sclerosis suffer occasional damage to a myelin sheath, but that such damage does not become progressively worse, despite the release of sulfatide.

It may be that the immune system of those who do not suffer with multiple sclerosis is better able to shut down inflammation and prevent the vicious cycle from developing.

Perhaps by providing supplemental NF-kB inhibitors we could prevent self-perpetuating inflammation in multiple sclerosis, or at least reduce the severity of that inflammation – thereby lessening damage and speeding the onset of remission.

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Profound improvement in psoriasis

Topical or systemic application of extract results in profound improvement in mouse model of psoriasis.

This publication is really quite remarkable.

First, it’s seldom that researchers will use a phrase like “profound improvement.” Researchers tend toward understatement, not hyperbole. The mouse must truly have been ‘cured’ to elicit such a statement.

Second, the extract was equally effective whether applied topically, or administered systemically.

Finally, this effect was achieved with an extract that has been in use for thousands of years.

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Psoriasis – eat a sponge?

Avarol, extracted from a sea sponge, inhibits NF-kB and so improves psoriasis.

NF-kB activation is decreased in the skin when avarol is applied, leading to reduced inflammation and improvement in psoriasis.

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Psoriasis dispute resolved

t seems there has been a dispute among psoriasis experts. Which is more important – the keratinocyte or the immunocyte.

It further seems that neither NF-kB activation in the keratinocyte alone, nor in the immunnocyte alone, resulted in psoriasis. However, when NF-kB is over activated in both – psoriasis results.

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NF-kB: Autoimmunity Master Switch

The abstract below does not say much. It merely suggests the central importance of NF-kB and then provides a very partial list of the autoimmune conditions for which NF-kB activation is central.

However, the full text article is a good overview, and is available free online.

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Colorectal cancer and inflammatory bowel disease

Over-activation of NF-kB is now recognized as a major contributor to inflammatory bowel disease and cancer. NF-kB activation results in inflammation, obviously of significance in inflammatory bowel disease, but increasingly recognized as central to carcinogenesis.

The relative cancer risk increases with the duration and severity of inflammatory bowel disease.

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Elemental diet effective for Crohn’s disease

An elemental diet is limited to basic nutrients in liquid form. No protein is included in the diet. Individual amino acids, the building blocks of proteins, are provided instead.

An elemental diet has found to be effective in Crohn’s disease, but for unknown reasons.

The authors of the study below investigated the role of histidine – an amino acid – in relieving colitis. They found that histidine reduced NF-kB activation in macrophages. Another amino acid, alanine, had no such effect.

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Probiotics for Crohn’s disease and ulcerative colitis

The term “probiotic” is used to describe organisms that are used medicinally, including bacteria such as Lactobacillus.

Lactobacillus bacteria are normally found in the small intestine. These are ‘good bacteria’ since they produce vitamin K as well as certain anti-microbial substances which prevent the ‘overgrowth’ of harmful bacteria.

A number of human trials have reported benefits associated with lactobacillus administration for the inflammatory bowel conditions ulcerative colitis and Crohn’s disease.

While lactobacillus is generally helpful, the specific means by which it benefits patients with inflammatory bowel disease was uncertain. Researchers have now determined that lactobacillus exerts it anti-colitis effect through inhibition of NF-kB.

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