Hi Laura...Ah, a lovely mornong in Brunswick Georgia..the sun rising slowly in the misty glow of The Waffle House signs across the parking lot.
Awaken sojourner.... oh lookee here. That interesting presentation got posted. I was wondering when it would pop up (and how soon it would be the subject of wild inference and implication). SO far no wild interpretations so thats good. Gee. Ya go on the road and ya miss the fun stuff.
Let me try to place this really interesting, but not new, info into some perspective. Lookoing at it in a vacuum born of unawareness of other data can make it confusing, or lead to odd postulates.In regards to the question you posted about the gut mast cells, we need to back pedal abit first: __________________________________________"...regarding what you posted, is the only way to decrease the mast cells through decreasing the anxiety, or is there another way?" __________________________________________...it is classic "postulating in a vacuum", and interpretation of the data I suspect will be the classic "bias dysinterpretation" that happens so often with much of the work done on IBS subjects (heck with everything done during the investigations into "syndromes").In this case, the study is very sound, but is destined for wild presumption...but the abstract is partly to blame for this.For example... ________________________________"It is well recognised that allergy and inflammation activate mucosal mastcells." ________________________________The context of the phrase "activate mast cells" has 2 meanings, so one has to figure out from the aims of the study and the use of the King's English in th U.K. whether the investigator means "activation" in terms of mediator release (degranulation) or in terms of "recruitment", or, mast cells "migrating" to a site of chronic insult as they are prone to do, thus over time mast cell density per unit of tissue can increase in a mucosla location such as the small or large bowel, and specific areas in the small or large bowel.Also, the literature for many years has been blessed with investigations of mast cell density within various gut location, usually with IBS patients they have looked at diarrheics, regardless of precursor events (did not separate post-infection IBS from IBS not preceded by an infection or other obvious "inflammatogenic insult"). It has been found several times that mast cell density was increased compared to controls. This has been studied and seen at the ileocecal junction, the outflow tract of the small bowel into the large bowel. So this is not new hence this may be what the author intends to say.However….. ----------------------------------"However, psychological stress can also activate mucosal mast cells in bothhumans & animal models. ---------------------------------….stress response is known, like "allergy" or several "inflammation" mechanisms as he already said, to precipitate degranulation….or lower the stimulus threshold of degranulation. But there is no clear record anywhere of "stress" causing mast cells to migrate to a specific area of the mucosa…so one at this point begins to wonder what the authors intent is. This we find out later from the protocol.He goes on…"IBS is often associated with psychiatric co-morbidity, both interms of previously treated illness and ongoing symptoms."---------------------------Indeed it is pretty much boilerplate to simply state the obvious, that IBS victims suffer psychological problems and associated increased anxiety, fear, and all manner of negativity as a consequence of livign with the symptoms and this increases the degree of stress the organism enbdures and that this secondarily can provoke symptoms further.----------------------------"Whether mast cells in rectalmucosa are related to anxiety in IBS is unknown."--------------------------So here the last comment still leaves us wondering what the context of "related" means. We already KNOW that mast cells and even circulatin immunocytes ARE "related to IBS as they are shown to both "activated" (lymphocytes and other circulating classes as well as mast cells are releasing mediators in response to specific dietary provocation which varoes from patient to patient and that reactivity is exacerbated by stress) and that mast cells migrate to locations of chronic insult within the bowel.Now the authors did (2) things clever…first they took the two IBS obvious subclasses and divided them up in a way others have not done…c-types from d-types which are subdivided into those where a known precursor event which activated the gut immune system occurred (infection). This way you can see if there are any distinguishing characteristics between these three groups as many have suggested previously.And they picked good markers of lymphocyte response, mast cell response (mediator release markers) and they checked the tissue biopsies as they are routinely done and compared that to looking closely at mast cell density.Now, skipping the technical jargon, they confirmed much of what is already known but found little if anything new EXCEPT that they did find there is a distinct difference between the c-types and the d-types as many have suggested…that this is a condition whereby the mechanisms, thus the condition, are distinct. Simply put, the diarrheics symptoms are linked to an abnormal inflammatory response of the mucosal and circulating immune system and the c-types do not show this. So its good as they confirm this. The c-types do not show signs of aberrant immune function.Now what was also nice is that it also confirmed what one would suspect….the post-infective IBS victims who have been postulated to suffer normal activation of the immune system in the bowel in response to infection but afterwards it persists, so the symptoms they experience persist are indeed shown to have persistent ec cell and lymphocytic activity but no tendency for mast cell density to increase. This is DISTINCT from the people who developed similar symptoms without a precursor infection, who showed cell mediated and mucosal immunocyte activation (mediator release) persisting combined with increasing numbers of mast cells in the mucosa. This is consistent with prior findings as well, except that someone finally checked the d-subtypes separately….and found this distinction. Which is consistent with other investigators findings and postulates in jejunal isolation and challenge in the upper GI where digestion tales place.This is a significant finding as well:----------------------------------"Anxiety levels were greater in IBS thancontrols mean 10.2 v 4 p less than 0.001 but not significantly different between the 3 patientgroups. "--------------------------------…in that it states the obvious has again been confirmed….living with aberrant bowel function is disquieting and can lead to the obvious consequences…followed by------------------------------"Mast cell counts increased with increasing anxiety levels p=0.015 with asignificant difference between severe anxiety and normal levels of anxiety 59.9 v 42.9p less than 0.001. "--------------------------But the mast cell counts in the c-types were the same as controls, and the post-infectious types showed the persistent infection-initiated inflammatory responses but also no increase in mast cell density. Only the non PI subpopulation showed this.So there is little if anything, if one has read ALL the available literature on the subjects of investigations into immune activation and in vivo and in vitro study of same in the IBS -symptomatic patient that suggests there is any cause-effect relationship between the levels of anxiety-based "stress" amd mast cell density. Especially since everyone had elevated levels of anxiety but on;y the non PI population of d-types showed increased mast cell density.So what is self evident is that indeed living with IBS symptoms increases anxiety, but the cart is before the horse if one tries to torturously imply, or the reader infer, that anxiety makes more mast cells migrate to the gut wall and park there. Rather for some reason some form of chronic insult/provocation linked to the non-PI subtype causes this to occur in these patients. What causes this to happen is well known, and if one looks at all the other work that has been kept in a vacuum when looking at these results (or maybe it has not been studied) there are people who show a weird allergy-like response of the gastric mucosa and circulating immunocytes including but not limited to t cell types, the response is provoked both episodically and continuously by patient-specific dietary components even though the patient has no circulating antibodies to the provoking agent, and the response can be heightened by anxiety related stress (and other sources of stress in the life of the victim) …and there is even evidence of a strange and heretofore unseen mast cell arming system (so far seen in jejunal isolation) which does include ,local IgE in some of the symptomatic patients…,which leads on to ponder would the distinguishing characteristic be the prior infection, as this would explain why some of the d-types and even normal patients have specific IgE in the jejunal washings absent circulating IgE and some do not but are still releasing mediators.But in no way does anything by any stretch of the imagination suggest that anxiety goeth before mast cell migration to the mucosa of any of the IBS subtype studied especially if you remove the data from the vacuum in which it is being considered relative to many years of other data collected while studying aberrant immune activation in IBS victims.So there is indeed nothing which suggests that altering or reducing anxiety elevels will reduce mucosal mast cell density since it shows no sign of being the origin of said pathology. Rather, reducing anxiety and stress WILL blunt the reactivity of the mast cells that are there, as well as the circulating immunocytes. But the more obvious tactic is to isolate and eliminate that which provokes them to release mediators which is extrinsic (the patient specific dietary provocateurs). Combine the two actions and you will achieve the best prophylaxis possible at this time and reduce or eliminate symptoms.This does not yet point to the etiologic basis for either the distinct pattern of persistent inflammatory response post infection, nor to the distinct abnormal inflammatory response of non-PI IBS victims. There are several ways in which this may occur in either population but much more work is needed to be able to isolate the "pathogenesis" on a population-specific basis. BUT at least the provider who has the tools needed to address that which provokes the responses can establish symptomatic prophylaxis on the 2/3 of the IBS population which HAS these aberrant immunocyte "behaviors".This also shows more clearly than ever why different strategies must be used, and a different perspective taken, when dealing with c-types. The distinctions between the types are even more glaring as a benefit of this investigation.MNL