Acute inflammation is often beneficial but can also be detrimental to the host, depending on its cause, severity, duration and specific circumstances. For example, acute inflammation is often responsible for much of the permanent damage that occurs as a result of heart attacks and strokes. Acute inflammation can also exacerbate pre-existing conditions, such as by precipitating asthma attacks, migraine headaches or seizures in those suffering from the underlying malady.
Chronic inflammation is always detrimental
Whereas acute inflammation can be either beneficial or detrimental, chronic inflammation always involves detriment to the host.
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There are at least 80 autoimmune related diseases, with new conditions being added frequently.
The National Institutes of Health estimates that five to eight percent of Americans have an autoimmune disorder.
75% of those with autoimmune disease are women, but some autoimmune disorders are more frequent in men.
Approximately 15% of all autoimmune patients have two or more autoimmune diseases.
As per the NIH, type I diabetes, multiple sclerosis, lupus, and psoriasis have combined annual direct medical cost of up to $20 billion per year.
Americans spend an estimated $87 billion each year in the treatment of autoimmune disease.
Autoimmune diseases are among the ten leading causes of death among women in all age groups up to 65.
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Results In each of the two Phase 3 trials, patients were randomized to one of three treatment groups: there was a 10mg/kg group, a 1 mg/kg group and a placebo group. Patients received an intravenous dose on days 0, 14 and 28, then every 28 days thereafter for the duration of the study. All patients…
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Irritable bowel syndrome is associated with an increase in circulating pro-inflammatory cytokines, including IL-8.
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Neuropathic pain is a current reality for up to 25% of the 20 million Americans with diabetes. However, of all those with diabetes, approximately half will eventually develop diabetic neuropathy.
Diabetic neuropathy is an extremely common complication of diabetes and results in pain and numbness that can affect the individual’s sleep, function, sense of well being and overall quality of life. The pain is often accompanied by unpleasant sensations such as tingling and burning. The pain may range from sharp stabbing pain to a consistent dull ache.
Neuropathic pain was previously called “non-inflammatory” pain, because it was thought to be…
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Unlike most other auto-immune disease, those with Sjogren’s do not experience relapses and remissions. That is, patients do not have periods of relatively high disease activity with intervening times of no or little active disease.
Why, among all auto-immune conditions, is Sjogren’s characterized by a steadily progressive course?
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Approximately half of those with multiple sclerosis (48%) are reported to experience chronic pain in association with their condition. Severe, chronic fatigue is reported by 75% of those with multiple sclerosis.
Multiple sclerosis is characterized by areas of demyelination (lesions) in the central nervous system (CNS: the brain and spinal cord.) It is believed that lesions in the CNS result when auto-antibodies specific to myelin attack and destroy the protective covering that surrounds the nerve fibers in the CNS.
The presence of CNS lesions can account for many of the unique symptoms of multiple sclerosis, but in many instances cannot explain…
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Among other symptoms, lupus is often characterized by pain and fatigue. The fatigue may be debilitating, and is often reported to cause greater impairment and greater loss of quality of life than does the pain.
Like most auto-immune conditions, lupus patients generally experience times of remission – times when disease activity is reduced. Among those lupus patients for whom pain is an issue, the severity of pain will generally diminish during remission and may cease altogether.
However, fatigue generally remains, even during an extended period of remission. Given that fatigue accounts for a substantial portion of the disability of lupus, this is of great concern.
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A long time ago – nearly 25 years ago in fact (ouch!) and just after graduating from college, I went on a three week canoe trip in the Boundary Waters Canoe Area (BWCA) up in Northern Minnesota.
Towards the end of that trip my hands became very inflamed – mostly the back of my hands. The inflammation was fairly extreme. So much so that it was limiting my ability to paddle – and my hands hurt.
I had earlier gouged my side on a tree branch during a portage. Don’t ask me why, but for some reason I connected the two, thinking that the wound plus continuous sun exposure was causing the hand inflammation.
I assumed that once the trip was over my hands would get better. But they didn’t.
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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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Corticosteroids are powerful anti-inflammatory agents that are often used to treat acute exacerbations of inflammatory conditions, such as ‘flares’ in multiple sclerosis. In the study briefly summarized below, methylprednisolone (corticosteroid) administration in multiple sclerosis patients (pulsed therapy) resulted in clinical improvement. That clinical improvement correlated with NF-kappaB inhibition. NF-kappaB is like a ‘master switch’ for…
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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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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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Inhibition of NF-kappaB was found to be effective in preventing relapse in a mouse model of multiple sclerosis. The publication:
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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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Variation in genes controlling inhibitors of NF-kB strongly influences susceptibility to multiple sclerosis.
Multiple sclerosis 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.
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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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Traditional Chinese medications used in the treatment of migraine are shown to inhibit NF-kB.
The authors suggest that traditional Chinese medications are effective in the treatment of migraine because they inhibit NF-kB.
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CNS regulation of peripheral inflammation, implications in fibromyalgia?
The central nervous system (CNS = brain and spinal cord) can regulate peripheral inflammation, but the pathways and mechanisms by which it does so remain unclear.
The study summarized below investigates the possibility that the neurotransmitter acetylcholine (ACh) exerts an anti-inflammatory effect via binding to a specific receptor found primarily on the synovial lining of rheumatoid arthritis and osteoarthritis joints.
That possibility is confirmed by observations of reduced pro-inflammatory cytokine activity as a result of such binding.
While the authors suggest that the receptor identified in rheumatoid arthritis and osteoarthritis joints might be a potential target for drug development, I am curious if a similar mechanism might explain the connection between observed neurotransmitter abnormalities seen in fibromyalgia and the persistence of peripheral inflammation.
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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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