Background: Objective assessment of inflammatory reactions in the gastrointestinal tract could be useful in the diagnosis of food hypersensitivity. The aim of the present study was to investigate the involvement of eosinophils and mast cells in the inflammatory response of patients with food hypersensitivity before and after food challenges. Methods: Eleven patients (4 with IgE-mediated allergy and 7 without) with food hypersensitivity and positive double-blind, placebo-controlled food challenge were subjected to food challenge in a single-blinded fashion. Four subjects with no known food hypersensitivity were recruited as controls. Placebo was given after a 1-week washout period followed by an active dose. Stool, urinary and serum samples were collected and symptoms were recorded in a diary. Fecal samples were analyzed for eosinophil protein X (F-EPX) and tryptase; urinary samples for EPX (U-EPX) and leukotriene E4 (U-LTE4) and serum samples were analyzed for eotaxin and food-specific IgE antibodies. Results: Patients with IgE-mediated food allergy had increased levels of F-EPX compared to controls and tended to have lower serum levels of eotaxin compared to non-allergic patients and controls. U-LTE4 was significantly higher in allergic patients compared to non-allergic patients after challenge. Moreover, F-EPX correlated to U-LTE4 (p = 0.011). Reported symptoms, abdominal pain, distension, flatulence and nausea were similar in the allergic and non-allergic patients. Conclusion: The results strongly indicate that eosinophils are activated in the gastrointestinal tract of food-allergic patients but not in patients with non-allergic food hypersensitivity. Due to the inconsistent pattern of symptoms after placebo and active food challenge, it was not possible to relate the levels of inflammation markers to the recorded symptoms.

Zuberbier T, Edenharter G, Worm M, Ehlers I, Reimann S, Hantke T, Roehr CC, Bergmann KE, Niggemann B: Prevalence of adverse reactions to food in Germany – a population study. Allergy 2004;59:338–345.
Young E, Stoneham MD, Petruckevitch A, Barton J, Rona R: A population study of food intolerance. Lancet 1994;343:1127–1130.
Crowe SE, Perdue MH: Gastrointestinal food hypersensitivity: basic mechanisms of pathophysiology. Gastroenterology 1992;103:1075–1095.
Bengtsson U, Nilsson-Balknas U, Hanson LA, Ahlstedt S: Double blind, placebo controlled food reactions do not correlate to IgE allergy in the diagnosis of staple food related gastrointestinal symptoms. Gut 1996;39:130–135.
Bischoff SC, Mayer J, Wedemeyer J, Meier PN, Zeck-Kapp G, Wedi B, Kapp A, Cetin Y, Gebel M, Manns MP: Colonoscopic allergen provocation (COLAP): a new diagnostic approach for gastrointestinal food allergy. Gut 1997;40:745–753.
van Ree R, Akkerdaas JH, van Leeuwen WA, Fernández-Rivas M, Asero R, Knul-Brettlova V, Knulst A, Aalberse RC: New perspectives for the diagnosis of food allergy. ACI Int 2000;12:7–12.
Bindslev-Jensen C, Ballmer-Weber BK, Bengtsson U, Blanco C, Ebner C, Hourihane J, Knulst AC, Moneret-Vautrin DA, Nekam K, Niggemann B, Osterballe M, Ortolani C, Ring J, Schnopp C, Werfel T: Standardization of food challenges in patients with immediate reactions to foods – position paper from the European Academy of Allergology and Clinical Immunology. Allergy 2004;59:690–697.
Ahlstedt S: Mediators in allergy diagnosis. ACI Int 1998;10:1–2.
Bengtsson U, Knutson TW, Knutson L, Dannaeus A, Hallgren R, Ahlstedt S: Eosinophil cationic protein and histamine after intestinal challenge in patients with cow’s milk intolerance. J Allergy Clin Immunol 1997;100:216–221.
Lin XP, Magnusson J, Ahlstedt S, Dahlman-Hoglund A, Hanson LL, Magnusson O, Bengtsson U, Telemo E: Local allergic reaction in food-hypersensitive adults despite a lack of systemic food-specific IgE. J Allergy Clin Immunol 2002;109:879–887.
Desreumaux P, Capron M: Eosinophils in allergic reactions. Curr Opin Immunol 1996;8:790–795.
Peterson CGB, Venge P: Purification and characterization of a new cationic protein- eosinophil protein-X (EPX) – from granules of human eosinophils. Immunology 1983;50:19–26.
Peterson CGB, Eklund E, Taha Y, Raab Y, Carlson M: A new method for the quantification of neutrophil and eosinophil cationic proteins in feces: establishment of normal levels and clinical application in patients with inflammatory bowel disease. Am J Gastroenterol 2002;97:1755–1762.
Lettesjö H, Hansson T, Peterson C, Ung KA, Ringström G, Abrahamsson H, Simrén M: Detection of inflammatory markers in stools from patients with irritable bowel syndrome and collagenous colitis. Scand J Gastroenterol 2006;41:54–59.
Magnusson J, Gellerstedt M, Ahlstedt S, Andersson B, Bengtsson U, Hansson T, Peterson C: A kinetic study in adults with food hypersensitivity assessed as eosinophil activation in fecal samples. Clin Exp Allergy 2003;33:1052–1059.
Peterson CGB, Lindgren D, Nyberg BI, Enander I, Rak S, Venge P: Measurement and characterization of eosinophil protein X (EPX) in urine. Eur Respir J 1995;8(suppl 19):228s.
Breuer K, Kapp A, Werfel T: Urine eosinophil protein X (EPX) is an in vitro parameter of inflammation in atopic dermatitis of the adult age. Allergy 2001;56:780–784.
Oymar K, Bjerknes R: Urinary eosinophil protein X in children with atopic dermatitis: relation to atopy and disease activity. Allergy 2000;55:964–968.
Kristjánsson S, Strannegård IL, Strannegård Ö, Peterson C, Enander I, Wennegren G: Urinary eosinophil protein X in children with atopic asthma: a useful marker of antiinflammatory treatment. J Allergy Clin Immunol 1996;97:1179–1187.
Gore C, Peterson CG, Kissen P, Simpson BM, Lowe LA, Woodcock A, Custovic A: Urinary eosinophilic protein X, atopy, and symptoms suggestive of allergic disease at 3 years of age. J Allergy Clin Immunol 2003;112:702–708.
Fasano A, Catassi C: Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology 2001;120:636–651.
Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Muller-Lissner SA: Functional bowel disorders and functional abdominal pain. Gut 1999;45(suppl 2):II43–II47.
Norgaard A, Bindslev-Jensen C: Egg and milk allergy in adults. Diagnosis and characterization. Allergy 1992;47:503–509.
Aas K, Backman A, Belin L, Weeke B: Standardization of allergen extracts with appropriate methods. The combined use of skin prick testing and radio-allergosorbent tests. Allergy 1978;33:130–137.
Kristjansson G, Venge P, Wanders A, Loof L, Hallgren R: Clinical and subclinical intestinal inflammation assessed by the mucosal patch technique: studies of mucosal neutrophil and eosinophil activation in inflammatory bowel diseases and irritable bowel syndrome. Gut 2004;53:1806–1812.
Bischoff SC: Colonoscopic Allergen provocation (COLAP) – technique and results. ACI Int 1997;9:1–2.
Garcia Zepeda EA, Rothenberg ME, Ownbey RT, Celestin J, Leder P, Luster AD: Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia. Nat Med 1996;2:449–456.
Zimmermann N, Rothenberg ME: Receptor internalization is required for eotaxin-induced responses in human eosinophils. J Allergy Clin Immunol 2003;111:97–105.
Shaw RJ, Cromwell O, Kay AB: Preferential generation of leukotriene C4 by human eosinophils. Clin Exp Immunol 1984;56:716–722.
Bandeira-Melo C, Bozza PT, Weller PF: The cellular biology of eosinophil eicosanoid formation and function. J Allergy Clin Immunol 2002;109:393–400.
Macfarlane AJ, Dworski R, Sheller JR, Pavord ID, Barry KA, Barnes NC: Sputum cysteinyl leukotrienes increase 24 hours after allergen inhalation in atopic asthmatics. Am J Respir Crit Care Med 2000;161:1553–1558.
Chadwick VS, Chen W, Shu D, Paulus B, Bethwaite P, Tie A, Wilson I: Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology 2002;122:1778–1783.
Drossman DA, Camilleri M, Mayer EA, Whitehead WE: AGA technical review on irritable bowel syndrome. Gastroenterology 2002;123:2108–2131.
Sampson HA: Food allergy. 2. Diagnosis and management. J Allergy Clin Immunol 1999;103:981–989.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.