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The abstracts below may help when it comes to understanding why our kids

develop food sensitivities and how the gastro issues tie into .

Ann Oncol 2001;12 Suppl 2:S19-25 Books, LinkOut

Nerve-driven immunity: neuropeptides regulate cytokine secretion of T cells

and intestinal epithelial cells in a direct, powerful and contextual manner.

Levite M, Chowers Y.

Department of Immunology, The Weizmann Institute of Science, and the The

Sackler Faculty of Medicine, Tel Aviv University, Israel.

mia.levite@...

Throughout the body, immune cells of various types, both classical (such as

T-cells) and less recognized (such as intestinal epithelial cells) are

exposed to a variety of neurotransmitters secreted from local nerve fibers.

Moreover, immune cells express specific neurotransmitter receptors. Based on

the above we asked whether neurotransmitters. by direct interaction with

their receptors, can either evoke or block immune functions in general, and

cytokine secretion in particular. We found that several neuropeptides (SOM,

Sub P, CGRP and NPY), in nM concentration and in the absence of any

additional stimulatory molecules, induced a significant secretion of

cytokines from Th0, Th1 and Th2 antigen specific T-cells. Moreover, some

neuropeptides surprisingly drove committed Thl and Th2 populations to a

'forbidden' cytokine secretion: secretion of Th2 cytokines from Th1 cells,

and vice versa. We further found that SOM by itself markedly affected the

secretion of proinflammatory cytokines from intestinal epithelial cells,

which play a major role in the gut immunity in the mucosal defense against

invading microorganisms. Thus, somatostatin, through its specific receptor,

inhibits (> 90%) of the spontaneous, TNF-alpha or bacteria

(Salmonella)-induced secretion of IL-8 and IL-1beta from two intestinal

epithelial cell lines. Taken together, these observations suggest that

neuropeptides can by themselves induce both typical and atypical cytokine

secretion from T-cells and intestinal epithelial cells. Since a myriad of

immune reactivities are mediated by, and dependent on, specific cytokines

secreted from immune cells, the neuropeptide-induced effects may have

important implications for numerous physiological and pathological

conditions, including autoimmune diseases, chronic inflammation and

neoplasias.

PMID: 11762346 [PubMed - in process]

: Inflamm Res 2001 Oct;50(10):491-5 Related Articles, Books, LinkOut

Tissue cytokine and chemokine expression in inflammatory bowel disease.

McCormack G, Moriarty D, O'Donoghue DP, McCormick PA, Sheahan K, Baird AW.

The Conway Institute of Biomolecular and Biomedical Research, University

College, Dublin, Ireland.

OBJECTIVE AND DESIGN: This study aimed to determine if mucosal expression of

the chemokines IL-8, RANTES and MCP-1 and the pro-inflammatory cytokines

TNFalpha and IL-6 are elevated in patients with inflammatory bowel disease.

MATERIALS AND SUBJECTS: Intestinal mucosa samples were obtained at the time

of surgical resection, n = 16 from each of the following groups:

normal/control, CD and UC. METHODS: An homogenate was prepared of each

tissue sample and cytokines measured by ELISA. RESULTS: IL-8 was

significantly increased in both disease groups compared to controls

Similarly, RANTES levels were also significantly increased. MCP-1 levels

were increased in both disease groups, this increase was statistically

significant in the UC group only. TNFalpha and IL-6 were significantly

increased in the CD group only. CONCLUSIONS: Chemokines, together with key

cytokines that promote their release are elevated in mucosal tissues from

patients with IBD. It is likely that these chemokines play an important role

in the perpetuation of tissue destructive inflammatory processes.

PMID: 11713901 [PubMed - in process]

: News Physiol Sci 2001 Dec;16:272-7 Related Articles, Books, LinkOut

Dysregulation of intestinal mucosal immunity: implications in inflammatory

bowel disease.

Laroux FS, Pavlick KP, Wolf RE, Grisham MB.

Departments of Molecular and Cellular Physiology and Medicine, Louisiana

State University Health Sciences Center, Shreveport, Louisiana 71130-3932.

The mucosal interstitia of the intestine and colon are continuously exposed

to large amounts of dietary and microbial antigens. Fortunately, the mucosal

immune system has evolved efficient mechanisms to distinguish potentially

pathogenic from nonpathological antigens. There are, however, situations in

which this immune regulation fails, resulting in chronic gut inflammation.

PMID: 11719604 [PubMed - in process]

--------------------------------------------------------------------------------

Crit Rev Immunol 2001;21(1-3):121-31 Related Articles, Books

Peripheral nonresponsiveness to orally administered soluble protein

antigens.

Nagler- C, Shi HN.

Mucosal Immunology Laboratory, Mass. General Hospital East and Harvard

Medical School, town 02129, USA. nagler_a@...

The presentation of soluble model food antigens to the intestinal immune

system typically induces antigen-specific systemic nonresponsiveness. Yet,

the gut-associated lymphoid tissue (GALT) must launch an effective attack

against potentially invasive pathogens even as it avoids mounting a response

to innocuous food antigens. Although the mechanism by which the GALT is able

to recognize and respond to these different forms of antigen is not clear,

recent studies have shown that, initially, both tolerogenic and immunogenic

forms of orally administered antigen elicit transient T-cell activation and

proliferation. The unique microenvironment of the GALT plays a central role

in determining whether functional T-cell anergy or adaptive immunity is the

ultimate response. Administration of model food proteins with adjuvants

(microbial products that activate the innate immune system) induces a

productive immune response to this normally tolerogenic form of antigen.

Recent work from our laboratory has shown that an ongoing enteric infection

can itself act as an adjuvant and prime for a response to an orally

administered soluble protein antigen.

PMID: 11642599 [PubMed - in process]

--------------------------------------------------------------------------------

Immunol Rev 2001 Feb;179:139-55 Related Articles, Books

Gastrointestinal eosinophils.

Rothenberg ME, Mishra A, Brandt EB, Hogan SP.

Department of Pediatrics, Children's Hospital Medical Center, Cincinnati,

Ohio 45229-3039, USA. Rothenberg@...

The gut-associated lymphoid tissue (GALT) is composed of lymphocytes

residing in Peyer's patches, lamina propria, and intraepithelial

compartments. In addition to these features which distinguish GALT from

other peripheral sites of the immune system, the gastrointestinal immune

system is also composed of resident eosinophils. Eosinophils are generally

considered to be peripheral blood leukocytes that have an important

pro-inflammatory role in various immune disorders. Although most research

concerning this cell has focused on understanding its trafficking and

function in the blood and lung, recent studies have also started to

elucidate its regulation and function in the gastrointestinal tract.

Interestingly, eosinophil numbers in the gastrointestinal tract are

substantially higher than in other tissues. At baseline (healthy

conditions), most eosinophils reside in the lamina propria in the stomach

and intestine. Eosinophil homing to these sites occurs during embryonic

development and their levels in perinatal mice are comparable to those in

adults, indicating that their homing is not dependent upon the presence of

intestinal flora. Furthermore, eosinophil localization to the lamina propria

at baseline is critically regulated by eotaxin, a chemokine constitutively

expressed throughout the gastrointestinal tract. Although eotaxin is

required for eosinophil homing, its expression in the esophagus is not

sufficient for eosinophil accumulation, since this organ is devoid of

eosinophils at baseline. During Th2-associated inflammatory conditions (e.g.

interleukin (IL)-5 overexpression or oral allergen challenge), marked

increases of eosinophils occur not only in the lamina propria but also in

Peyer's patches. The accumulation of Peyer's patch eosinophils, which mainly

occurs in the outer cortex and interfollicular regions, is critically

regulated by IL-5 and less significantly by eotaxin, suggesting the

involvement of other eosinophil chemokines in this lymphoid compartment.

Preliminary investigations have shown that gastrointestinal eosinophils

express the alpha4beta7 integrin and that this molecule is responsible, in

part, for eosinophil homing. In summary, eosinophils are resident cells of

the gastrointestinal immune system whose levels can be induced by antigen

exposure under Th2 conditions, in a manner that is critically regulated by

eotaxin and IL-5. We propose that eosinophils are integral members of the

gastrointestinal immune system and are likely to be important in innate,

regulatory and inflammatory immune responses.

Publication Types:

Review

Review, Academic

PMID: 11292017 [PubMed - indexed for MEDLINE]

Allergy 2001;56 Suppl 67:12-5 Related Articles, Books, LinkOut

Oral tolerance to protein antigens.

Mayer L, Sperber K, Chan L, Child J, Toy L.

Mount Sinai Medical Center, Immunobiology Center, New York, NY, USA.

lloyd.mayer@...

Oral tolerance is an active non-response to antigens delivered via the oral

route. Mechanisms governing tolerance induction have been well characterized

in mouse. Similar studies in man are lacking, although there is evidence

that tolerance can be induced. In disease states, tolerance is altered and

this may account for the presence of mucosal inflammation. In food

hypersensitivity there is evidence that allergens may be handled differently

and this may play a role in disease expression.

Publication Types:

Review

Review, Tutorial

PMID: 11297999 [PubMed - indexed for MEDLINE]

--------------------------------------------------------------------------------

: J Allergy Clin Immunol 2000 Nov;106(5 Suppl):S251-7 Related Articles,

Books, LinkOut

Determinants of systemic manifestations of food allergy.

Sicherer SH.

Elliot and Roslyn Jaffe Food Allergy Institute, Division of Allergy and

Immunology, Department of Pediatrics, Mount Sinai School of Medicine, New

York, NY, USA.

The myriad of systemic manifestations induced by food hypersensitivity

responses is testament to the ability of localized exposure to foods in the

gastrointestinal tract to result in symptoms in distal target organs. Cow's

milk protein, for example, may induce hives (urticaria), atopic dermatitis,

isolated gastrointestinal symptoms, or severe generalized anaphylaxis in

different individuals or in the same person at different times. These

diverse manifestations are the result of complex interactions among the

causal food protein, gut, immune system, and target organs. The dynamic

state of these interactions is demonstrated by the development of food

tolerance in most subjects and by the ability to experience the development

of new allergies in some subjects. This review explores the variety of

clinical manifestations of food hypersensitivity disorders in the context of

the question: What determines the local or systemic expression of food

allergy in a given individual at a particular time? Evidence is provided for

both systemic and local immune activation. The role of food-protein

chemistry, absorption and processing of ingested allergen, immune responses

(type, degree, and specificity), and target organ hyperreactivity are

considered as determinants in the expression of food allergic disorders.

Publication Types:

Review

Review, Tutorial

PMID: 11080740 [PubMed - indexed for MEDLINE]

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