Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017160 (gastroenteritis)
 11,398 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eosinophil infiltration into the esophagus is observed in diverse diseases including gastroesophageal reflux and allergic gastroenteritis, but the processes involved are largely unknown. We now report an original model of experimental esophagitis induced by exposure of mice to respiratory allergen. Allergen-challenged mice develop marked levels of esophageal eosinophils, free eosinophil granules, and epithelial cell hyperplasia, features that mimic the human disorders. Interestingly, exposure of mice to oral or intragastric allergen does not promote eosinophilic esophagitis, indicating that hypersensitivity in the esophagus occurs with simultaneous development of pulmonary inflammation. Furthermore, in the absence of eotaxin, eosinophil recruitment is attenuated, whereas in the absence of IL-5, eosinophil accumulation and epithelial hyperplasia are ablated. These results establish a pathophysiological connection between allergic hypersensitivity responses in the lung and esophagus and demonstrate an etiologic role for inhaled allergens and eosinophils in gastrointestinal inflammation.
 ...
PMID:An etiological role for aeroallergens and eosinophils in experimental esophagitis. 1113 83

The mechanisms responsible for sensitization, in particular within the gastrointestinal tract, are IgE-mediated as well as of a non-IgE-mediated, immunological origin. The phenomenon that is the opposite of sensitization is the maintenance of tolerance and is exemplified by the phenomenon 'oral tolerance'. The cytokines transforming growth factor beta and interferon gamma have been shown to be key immunoregulatory cytokines in oral tolerance. A new experimental model of eosinophilic allergic gastroenteritis has been developed with the use of encapsulated dietary antigen. The model was used in mice with genetic deletions of the eosinophil chemokine eotaxin or of the cytokine IL-5, demonstrating the importance of eotaxin. In clinical allergy research, a major question has been to explain the global increase in asthma and allergy. The 'hygiene hypothesis' states that a lack of maturation of the infant immune system from a T helper 2 to a T helper 1 type of immune response may be caused by less microbial stimulation in Western societies. Several lines of data support this hypothesis. However, apart from the genetic constitution of the individual, breastfeeding in infancy may be the most important single determinant for the development of clinical tolerance.
 ...
PMID:Sensitization and tolerance. 1196 95

Eosinophilic gastrointestinal disorders, including eosinophilic esophagitis, gastroenteritis, and colitis, refer to a spectrum of clinical diseases that present with variable degrees of infiltration of the gastrointestinal tract by eosinophils in the absence of other known causes of tissue eosinophilia. Clinical symptoms and laboratory findings are usually non-specific and may or may not be accompanied by peripheral blood eosinophilia. The extent of eosinophilic infiltration of the gastrointestinal wall varies from mucosal to transmural and serosal involvement. Diagnosis requires presence of gastrointestinal symptoms, demonstration of gastrointestinal eosinophilia by biopsy, and exclusion of other known causes of tissue eosinophilia. Many studies have pointed toward the eosinophil as the major offender; however, the exact functional role of the eosinophil in the pathogenesis of eosinophilic gastrointestinal disorders remains unclear. The roles of T-helper-2 cytokines and other mediators, such as eotaxin-1 and interleukin-5, have gained significant importance in the pathobiology of eosinophilic gastrointestinal disorders. Current understanding of treatment is based on case reports and a few case series, as there is a lack of large prospective studies. Steroids are currently the mainstay of therapy, but the roles of other drugs such as leukotriene inhibitors, mast cell stabilizers, interleukin-5 inhibitors, and anti-immunoglobulin E, along with other targets in the immune pathway, are currently being explored.
...
PMID:Eosinophilic Gastroenteritis and Colitis: a Comprehensive Review. 2605 22