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A recent guest post on kevinmd.com by Sophie Lee expressed her frustration and anger at physicians who dismiss her reports of pain with her severe bouts of irritable bowel syndrome (IBS). She repeatedly hears, “it isn’t really serious” “you will just have to live with it, etc.  [ www.ibstales.com ].

I just do not get why conventional “wisdom” is that IBS is not an inflammatory disorder. Perhaps pain is possible without inflammation, but that would be atypical. My contention is that if the immune system was in homeostasis, autoimmune disease would either not occur, or it would be limited.

For years I have been questioning “experts”, how is it that IBS is categorized as an autoimmune* disease, yet you claim there is no inflammatory response in the gut?

Current research supports my contention. Recent studies are providing evidence that low levels of inflammation, along with immune mast and other immune cells, are found in the small and large intestines. Mast cells are typically associated with allergic reactions such as runny noses, watery eyes, swelling, and excessive mucous. The mast cells in the intestines appear to be involved in immune homeostasis, in helping the immune system balance.

Interestingly, many of the immune cells found in the gut are in close proximity to nerve cells. .. “Cross-talk” between these cells may explain the pain and other symptoms that individuals experience, and support the hypothesis of a brain-gut axis event in IBS.

It is time for individuals that have “tried everything”, to give their bodies a chance to heal naturally. The immune system has caused the problem, and the immune system can be gently guided to down-regulate overly active responses.

The key to greater comfort may be as simple as helping the body return to immune homeostasis. I hold a patent in the area of immune homeostasis and gut health, and numerous anecdotal reports suggest that balancing immune inflammatory responses makes a major difference in the quality of life of such individuals. Additionally there is a published clinical report by Mark Morningstar, DC, Grand Blanc, MI supporting the relationship between immune homeostasis and healthy bowel function.

One has everything to gain by letting one’s own body rebalance and limit inflammatory responses.

*The immune system mistakenly attacks “self”, the body’s own healthy tissues.

ncbi.nlm.nih.gov/pubmed/22053295
sciencedaily.com/releases/2010/06/100607111308.htm
ncbi.nlm.nih.gov/pubmed/18627650
ncbi.nlm.nih.gov/pubmed/19674619
patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6,803,035.PN.&OS=PN/6,803,035&RS=PN/6,803,035

Recently, a professional networking site directed me to a short note by Lisa Moreno-Dickinson, President of the stopcaidnow.org. The title of her article was “When Doctors Don’t Know How to Help From Misdiagnosis to No diagnosis … What Can a Parent Do?”.

CAID refers to Childhood Auto Inflammatory Diseases. These genetic disorders usually start in infancy or childhood and are reported to be the result of gene mutations. The periodic attacks of these conditions affect many different organ systems. They are characterized by sudden inflammation and fever onset, and symptoms such as rashes, headache, abdominal, chest, muscle, and joint pains, swollen joints and scrotum.

Much of the science suggests that these conditions are not autoimmune in nature. These individuals have no any significant elevations of autoantibodies, immunoglobulins, large immune molecules that are directed against self, nor activation of specific white blood cells.

Our knowledge of the complexities of the immune system, especially its inflammatory pathways, are still in their infancy as supported by the fact that cancer, colds, infectious, and chronic diseases are rampant.

I respectfully suggest that perhaps autoinflammatory investigators have not used the appropriate assay to find autoimmune responses because a) it does not exist yet, or b) it is difficult to “test for everything”.

A recent report suggests that there is an association between autoinflammatory conditions and mitochondrial health. Mitochondria are the power stations of a cell that provides it with the energy it needs to grow, divide, and “do its job”. They play major roles in healthy aging, degenerative diseases, cancer, and ultimately, cell death. The greater its metabolic or energy requirements, the more mitochondria a cell appears to have. As an example, a muscle cell may have thousands of mitochondria and a skin cell only a few hundred.

Antibodies to mitochondrial proteins have been reported in autism spectrum disorders, which are attributed to inflammatory conditions of the nervous system. Additionally children with severe autism have higher levels of inflammatory cytokines and certain immune molecules than controls.

In Blau’s syndrome, an autoinflammatory disease, symptoms are associated with the skin, joints, and eyes. It is often mistaken for sarcoidosis, a known autoimmune disease of the skin and other organs. Crohn’s disease is an inflammatory autoimmune bowel disease in which the immune system attacks its own digestive lining.

There are two genes, NOD1 and NOD2 that help regulate the production pro-inflammatory cytokines, immune molecules that cause inflammation. Mutations of these genes are found in a number of inflammatory disorders including Blau’s syndrome, sarcoidosis, and inflammatory bowel diseases.

Investigations of the pivotal role of gene regulation of inflammatory responses are underway; however, ways to neutralize the effects of such mutations may be years away.

Parents and clinicians do not have the luxury of just waiting. We know that inappropriate inflammatory responses are occurring in many, so why not determine whether the re-introduction of immune homeostasis, immune balance would make a difference in their quality of life?

 

www.parentsociety.com/parenting/when-doctors-dont-know-what-to-do-or-how-to-help/?goback=%2Egde_151241_member_74525704

www.ncbi.nlm.nih.gov/pmc/articles/PMC2735099/

www.ncbi.nlm.nih.gov/pubmed/16466630

www.ncbi.nlm.nih.gov/pubmed/21453638

www.ncbi.nlm.nih.gov/pubmed/21083929

www.ncbi.nlm.nih.gov/pubmed/21735170

www.ncbi.nlm.nih.gov/pubmed/18368292

www.ncbi.nlm.nih.gov/pubmed/21521652

www.ncbi.nlm.nih.gov/pubmed/21433392

 

The Centers for Disease Control is investigating at least 100 reports of food poisoning, and 18 deaths, due to contaminated cantaloupes. DNA isolated from infected individuals has determined that Listeria is the responsible bacteria. Ninety-eight percent of 93 individuals contacted by monitoring agencies were hospitalized due to their infections. Because of lag times between consumption of these cantaloupes, illness, diagnosis, and laboratory confirmation, more cases are expected to occur.

Five percent of the human population has Listeria in its stool. It is also found in stools of non-human mammals, and birds. This may explain the fact that Listeria is found in water, soil, and animal feed.

Newborns, pregnant women, and individuals with immune disorders such as kidney disease, cancer, diabetes, and HIV/AIDS are at increased risk of becoming ill when infected with Listeria. In 89 % of cases, Listeria pass through the intestinal wall and enter the blood stream. From there, they are carried throughout the body and can end up in the brain, spinal cord, heart, eyes, liver, spleen, lungs, bones, and joints.

Instead of being attacked by immune cells, initially, Listeria hides in immune cells, multiplies, and infects other white blood cells. To stop the infection and return to immune balance, immune homeostasis, the body defends itself by releasing inflammatory and anti-inflammatory cytokines, cell messages, and antibodies, large proteins that mark the bacteria for destruction by inflammatory immune cells.

About half of adults with Listeria infection will be diagnosed with meningitis, an inflammatory condition of the brain and spinal cord. Endocarditis, inflammation of the inner lining of the heart, results in deaths of about 50% of patients.

So, ultimately, excessive inflammation kills infected individuals.

 

www.faqs.org/health/topics/74/Listeriosis.html#ixzz1ZgKQS5E5
www.cdc.gov/listeria/outbreaks/cantaloupes-jensen-farms/100411/index.html#introduction
www.ncbi.nlm.nih.gov/pubmed/21830209
www.ncbi.nlm.nih.gov/pubmed/8251578
www.experts.scival.com/mskcc/grantDetail.asp?t=ep1&id=373762&o_id=3&

Today, three immunologists, Drs. Ralph Steinman*, Jules Hoffman, and Bruce Beutler, won the Nobel Prize in Medicine/Physiology for adding to our scant knowledge of immune system responses to pathogenic microorganisms and cancer cells. Their studies should also provide a better understanding as to how excessive inflammation leads to autoimmunity, attacks on the body’s own healthy tissues.

Two decades ago Dr. Ralph Steinman and his colleague, Dr. Zanvil Alexander Cohn at the Center for Immunology and Immune Diseases, Rockefeller University in New York City, described dendritic cells, specialized immune cells that interact with other immune cells to define how the body will respond to underlying infection and disease.

Dendritic cells are essential to the body’s ability to control immune inflammatory homeostasis. Immune homeostasis is the delicate balance of all immune responses, especially inflammatory and anti-inflammatory responses, that that the body uses to fight disease. Too little inflammation may result in uncontrolled growth of pathogens or cancer cells, whereas too much inflammation, may result in autoimmune conditions such as diabetes, arthritis, lupus, multiple sclerosis, Crohn’s disease, etc.

Part of the role of immune homeostasis is to determine “what comes next” in meeting immune challenges. Dr. Steinman and his colleagues described an important phase of the immune response, “maturation”, which helps the body determine inflammatory and other responses to infection.

Dendritic cells are also important in helping the body maintain immunological “memory”. This assures a more rapid and thorough immune response if is attacked by the same pathogen another time. [Successful immunization depends on immunological memory.]

Dr. Jules Hoffman and his team, described how the immune system first recognizes invading pathogens and then helps trigger the immune system to go into its protective mode.

Dr. Beutler discovered the inflammatory cytokine, tumor necrosis factor, TNF, and a marker on certain bacterial cells that helps the body recognize that it has been infected, so that it can mount an appropriate inflammatory attack.

www.nobelprize.org/nobel_prizes/medicine/laureates/2011/press.pdf

www.rockefeller.edu/labheads/steinman/pdfs/2003-APMI.pdf

www.ncbi.nlm.nih.gov/pubmed/21960036

www.wrvo.fm/post/nobelists-showed-how-immune-defenses-work-and-go-awry

*The Nobel Committee has expressed “deep sadness and regret” at the news that Dr.
Steinman died a few days before its announcement.   Typically, the Nobel Prize is not awarded posthumously, but the Committee has decided to proceed with bestowing the award on Dr. Steinman.

Bernard Lown, MD The Lost Art of Healing Boston New York Houghton Mifflin Company 1996

Medicine in the United States is widely regarded as the best in the world*. Hardly a day passes without a major scientific breakthrough. Many formerly fatal diseases are now curable. People are healthier and live longer than ever. Still, patient dissatisfaction with doctors has rarely been more acute. Although physicians are increasingly able to cure disease and prolong life, the American public is suspicious, distrustful of, even antagonistic to, the profession. Doctors, uneasy, astonished, resentful, and angry, universally acknowledge a crisis in health care. With the focus on colossal medical expenditures, amounting to a trillion dollars annually, most of the numerous solutions involve containing runaway costs….

Medicine’s profound crisis, I believe, is only partially elated to ballooning costs, for the problem is far deeper than economics. In my view, the basic reason is that medicine has lost its way, if not its soul.

* And yet, depending on the Agency that sponsored the study on longevity, America ranks either 27 or 30th , in the world in terms of mortality. Countries like Malta and South Korea have longer life expectancies than individuals in the U.S.

Next week the United Nations will hold a unique Summit, the first one focusing on the worldwide chronic diseases such as diabetes, cancer, heart, and lung disease. These are also the major diseases that challenge Americans.

And it has become increasingly obvious that uncontrolled immune inflammatory responses are major contributors to disease. Inflammation results in illnesses of many types, and vice versa. For example in the case of cancer and inflammation, there is “cross talk” between immune and tumor cells with inflammatory responses playing major roles during different stages of tumor development.

The key to health is immune balance, immune homeostasis. Immune homeostasis is a state where the level of inflammatory cytokines, is inhibited by anti-inflammatory cytokines and other immune factors. The right ratio of these cell messages restores the body’s delicate immune balance, and lessens the likelihood that one will become ill. Controlling inflammation is a primary approach to decreasing chronic disease.

 

http://hdr.undp.org/en/statistics/

www.jci.org/articles/view/25102

www.ncbi.nlm.nih.gov/pmc/articles/PMC2866629/

 

An article this week from Shirley Wang, a Wall Street Journal reporter, brought the public’s attention back to the fact that there is no cure for the usually fatal disorder, amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. Amyotrophic lateral sclerosis (ALS) is a paralytic disease caused by the gradual degeneration of nerve cells in the brain and spinal cord. The breakdown of neruons interrupts the ability of muscles of the body to send messages to the brain. ALS results in difficulties in talking, swallowing, moving, and paralysis, and eventually, the loss of the ability to breathe.

An international group of scientists recently reported in the journal Nature, that the lack of a certain protein might be the common underlying cause of neurodegenerative diseases such as ALS, dementia, Parkinson’s, and Alzheimer’s. The task of this specialized protein is to remove the debris of damaged nerve cells and help in their repair. When this function no longer occurs, normal transmission of signals from muscles to brain is blocked.

One individual commented on Ms Wang’s article. “It seems outrageous to me that in 2011 a quickly fatal disease that was brought to our national attention in 1939 continues to steal our best and brightest without any treatment and with few clues as to the cause. We must do better….”

I agree. Instead of treating a condition after damage has occurred, why not prevent excessive inflammatory responses from causing damage in the first place? The ALS Association does an excellent job explaining that, “The glia cells that usually support and nourish their neighboring neurons in the nervous system can become over active in certain diseases”. And that leads to over production of cytokines, immune signals, that are mediators of inflammation,and damage to the nerve cells.

Inflammation protects the body from infection and repairs tissue damage. But uncontrolled levels of inflammation damages healthy by-stander cells, and tissues. When it comes to the repair protein mentioned above, perhaps individuals with ALS, or other neurodegenerative diseases, are attacking this protein, and decreasing the quantities needed for clean-up and repair.

A body in immune homeostasis, immune balance, is unlikely to attack itself. Instead one approach that research should take is finding ways to help the body modulate inappropriate levels of inflammation.

 

www.ninds.nih.gov/disorders/amyotrophiclateralsclerosis/detail_ALS.htm

www.chicagotribune.com/health/ct-met-northwestern-als-breakthrough-20110822,0,4185292.story

www.nature.com/nature/journal/v477/n7363/full/nature10353.html

http://www.alsa.org/research/about-als-research/inflammation.html

 

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