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Man, I could pound out info and references on this one all day....and have you and other readers reading and puzzling all day on how it all fits together. Instea lets cut to the chase with a very breif and simplified answer to your posted question.The bottom line is that for decades various investigators have been looking at the links between IBS symptom sets (primarily d-types and cyclic types of the population so far, which is about 70% of all the people diagnosed with IBS) and inflammatory responses to provocation in the small bowel as the most plausible explanation for these symptoms sets since it is the only scenarios which consistently fits all the pieces of the puzzel together biochemically.Some of the most obvious observations which have always pointed to this:They (the symptoms) fit perfectly what happens when the immunocytes associated with the bowels' immunoprotective functions are activated. Various types of inflammatory reactions can occur which result in shortened transit time, increased sensory perception, pain, increased secretion of fluid and reduced absorption, reduced response threshold of gut smooth muscle, non-gut symptoms related to activation of other neurons in the body besides those of the gut up to and including (depending upn which reaction occurs) very specific and general CNS ("brain tissue") activation.For many years now experiments have shown that in this subpopulation that some form of abnormal immune reaction occurs in the small bowel, and that it can be provoked by food or additives in foods and aggravated and perpatuated by behavioral responses both autonomous and learned.Symptoms can be reduced or eliminated by isolating and removing provoking dietery components, and can be attenuated to varying degrees with therapies that alter perception and stress response (ie CBT and HT for example). And when combined properly a greater degree of relief can be obtained than with single mode therapy since the involved gastroneuroimmunoendoexocrine systems are fully integrated and codependent.It has also been shown that the majority of the response of the immune system of the gut is not allergic in origin, but it appears about 8% of the IBS patients have comorbid true food allergies in addition to food and chemical provoked reactions of the small bowel. These predominating multi-pathway reactions are not mediated by the specific circulating immunoglobulins you can isolate with conventional allergy tests(the patients for example come back oral challenge positive, positive to provocation of circulating immunocytes like granulocytes, lyphocytes and platelets but negative by skin testing and such things as radioimmunoassaysa for specific immunoglobulins, exept for those with allergy comorbdity). This has been for decades a 'fascinoma'.Also, while the colon appears normal except for increased mast cell tissue density in some patients at the ileaocecal junction, there are irrefutable and clear confirmations of immunocyte involvemement in the gut. This first came in the form of consistent response to cell wall stabilizers like cromolyn sodium when taken by IBS patients of the d and cyclic type. if the immunocytes, esp. mast cells, were not involved then they would have no effect.These are substances used in asthmatics to stabilize the mast cells, to keep them from a process called "degranulaton". Their classic use has been in asthma, and in some cases IBD. The mucosa of the respiratory tract and small bowel are very similar in function and immune structure. The front line of defense is the "tissue" immune system dominated by the mast cells. They contain a storehouse of numerous preformed chemicals (including histamine and serotonin among many others) which are released when the mast cell is trigered to release them. This promotes a cascade of reactions of the immune system which are protective in intent. Also, once activated, there are other mediators that are synthesized from pieces-parts and added to the mix of preformed mast cell mediators.The circulating immunocytes (lymphocyte types, granulocyte types, platelets and macrophages) may also be invoked to act via various mechanisms. Their mediators are also released...they are "cytoprotective" proinflammatory mediators as well. The idea is to discriminate between danger (pathogens) and safe (food and drink) and respond to danger with attack and evacuation (removal) and to remain silent when safe things are present.So for many years it has been shown over and over again that the mast cells of the small bowel are being activated in these IBS patients, and that they can be and are being abnormally provoked by dietary components. Though nobody knows yet all the possible reasons WHY they start to misbehave, the markers of mast cell and circulating immunocyte reaction can be and have been recovered from the fluids within the small bowel and the markers of circulating immunocytes reactions, including accumulations of the cells themselves at the root ganglia even, can be seen on biopsy.Again, this all happens even in IBS patients who are allergy-negative. So the mucosal reaction (mast cells are at the root of it) is King so to speak and the circulating immunocytes are subjects (vasals) in a way, BUT they are also summoned independently of the King (they do not rely upon mast cell degranulation to react...this can be demonstarted any day of the week in vitro...healthy peoples immunocytes do not react to to non-chemotoxic foods or additives in vitro and patients with symptoms of such conditions as IBS and migraine and asthma and FMS DO react to safe things both in vivo and in vitro).The symptoms experienced are collateral damage...side effects of the mediators either intentional as part of the protective mechanisms being invoked specifically, or as untoward effects...consequences of releasing that chemical to activate Process A causes Tissue B to respond in the desired way but Tissue C is also effected as a consequence and this is an undesireable but temporary effect. And even when Tissue B responds positively an untoward efect usually accompanies the esired effect. It's like Joker said "If you want to make an omelet you have got to crack some eggs!". If you want to contain and kill and remove pathogens you are going to offend some normal tissue or processes when you act.This is a good book to read to try to get a picture of the myriad immune mechanisms and mediators (including mast cells) and interractive functions, as least as much as is known so far (there is much that is not understood you will see the more you read):The Immune System by Peter Parham http://www.amazon.com/exec/obidos/ASIN/081...4326764-6290107 and this is a good book to read to understand the role of the immune system structures in disease:"FOOD ALLERGIES AND FOOD INTOLERANCE: THE COMPLETE GUIDE TO THEIR IDENTIFICTION AND TREATMENT", Professor Jonathan Brostoff (M.D.. Allergy, Immunology and Environmental Medicine, Kings' College, London) http://www.amazon.com/exec/obidos/ASIN/089...6487508-3420903 So is this, if you can find one. It is a medical reference text for physicians which is out of print now, but a new edition is in editing at this time with updated info. These are sometimes locatable in the medical library or used:Food Allergy and Intolerance- by Jonathan Brostoff, Stephen J. Challacombe http://www.amazon.com/exec/obidos/ASIN/070...2580864-1502269 The mast cell is so effective as a protective structure, and so dangerous, because of where it sits in the gut wall...if you look at the gut wall structures you will see those babaies an the enterocromafin cells sitting right there with the gut nerves and smooth muscle and vasculature. They have to be as they must act directly upon them when provoked to do so.Now interestingly, it has been very difficult to understand why the mast cells begin to misidentify safe things like foods or safe additives as dangerous and degranulate without the specific immunoglobnulins to the substance cirulating around (except in the case of pseudoallergic response where the chemical reaction is direct, like from lectin which can plug right into the cell and trigger it to go BOOM). Also, why the circulating immunocytes down there in the microvasculature of the bowel are also responding...independently. Now those are easier to explain when you look at things like the alternate complement pathway and cytotoxic reactions and several other pathways and how permeability is altered in response to mast cell mediators (to let more immonytes get to the apparant site of danger OUTSIDE the capillaries)thus how this can lead to the wrong kind of immune complexes being formed ad nauseum, but why the mast cells misidentify things absent detectible immunoglobulins to things has been puzzling.However, in Sweden they have recently discovered (among the many mediators that can be recovered from the small bowel washings in the IBS patients studied by jejunal isolation) was....IgE?. So these allergists are now pondering if the whole thing is some kind of localized IgE mediated reaction...that is, there actaully are specific immunoglobulins involved but they do not circulate around so that is why SPT and RAST and ELISA do not show any signs of them.Trouble that complicates it is that they found some of the same thing in non-symptomatic patients...so the mast cells may be naturally prearmed, or prearmed under certain conditions and the preconditions, and something else discriminates the ones that remain stable from those which do not...reactive patients which show off with IBS and those that do not. It is very unclear, though, at this time. This stage of investigation has just finally been reached, as this is not exactly a benign thing to do to someone (jejunal and duodenal isolation and challenge). Not to mention wh funds such things? So far just certain Swedish medical centers, nd maybe the Italians will jump on it now too. These are hotbeds of investigation into preventive or prophylactic medicine.But what is clear as a bell is that these bad boys are a major player in at least so far the subpopulation (70%)of the d's and cyclics, and what can trigger them to go off can be isolated and thus avoided. Also that things which stabilize mast cells and other immunocytes reduce symptoms proportionate to the array of cells they are effective on (cromolyn soidum works alot better on mast cells than granulocytes, so they can stop the mast cell response but only blunt the granulocyte response...this was seena s far back as 1988 where it was discussed at the 47th annual conference of the American College of Allergy and Immunology [everybody knew that CS worked on mast cells but it was first shown that it could blunt granulocyte response some also when the patients suffered non IgE food reactivity]. Oh before you jump up and aay 'Why don't we just give everyone CS...let me answer: tachyphylaxis.
Bummer.Another interesting thing about mast cells is that they localize...that is if there is a site of the body of chronic danger, chronic provocation, the number of mast cells in the tissue will increase. Conversely if the number of mast cells increases inappropriately and they are unstable then that site paradoxically becomes a site of chronic inflammation.A number of times (I cannot remember the count I would ahve to go back anf look) it has been noted that many IBS victims show increased tissue mast cell density at the ileocecal junction...the place in the large bowel where the small bowel empties into the large bowel. This signifies a sight of chronic provocation of some sort.
Anyway we can go on and on and on...I hope that puts some of Mr. mast cell into fairly plain english. He is largely responsible for IBS being referred to by some as "asthma of the gut" due to the similarities seen between the two immune responses. And as we know one is sometimes a comorbidity of the other. editorially, it's funny how so many of the comorbidities of IBS are conditions which are linked by the common thread of aberrant immune response. Yet there are those who persist in citing immunologists and allergists who wave the smoking guns as nothing but cowboys, so to speak. Or just totally ignore it as it does not fit their own line of thought or theories or line of funded investigation.But the consept is so simple...if an aberrant immune rsponse was not implicated in the symptoms of the 70% of IBS victoms with diaarheic and cyclic diarrhea and constipation, then thse apteints would NOT respond to variosu immunomodulators NOR would there be proinflammatory mediators in the small bowel washings NOR would there be clear tissue signs of chronic immunocyte activaton on small bowel biopsy NOR would their circualting immunocytes discharge mediators in vitro when exposed to safe substances as opposed to normal peoples immunocytes which do not.As Grouch Said, "It's so simple a child of five would understand this. Send someone to fetch a child of five."
Eat well. Think well. be well. (Don't degranulate)MNL