Eosinophils in Inflammatory Bowel Disease

Eosinophils in Inflammatory Bowel Disease

Benjamin J Schaus, Shen Bo
US Gastroenterology Review 2007 - Issue I - March 2007
Published: October 2008
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The etiology and pathogenesis of inflammatory bowel disease (IBD) is still unclear. It is generally believed that IBD results from abnormal interactions between gut microflora and the deregulated host’s immune response in genetically susceptible individuals.1–3 There is an increase in the number of inflammatory cells in inflamed gut mucosa in patients with IBD, including plasma cells, T-lymphocytes, macrophages, mast cells, neutrophils, and eosinophils. Accumulated evidence suggests that eosinophils play an important role in IBD. Histopathological observations demonstrate eosinophils and their related proteins in increased quantities in the mucosa of IBD patients. Accumulation of eosinophils is also seen in asthma, allergy, parasitic infections, and certain neoplasms.4 While the pathogenetic role of eosinophils in allergy4 and asthma5 has been extensively studied, the contribution of these cells in the pathogenesis of IBD is still under investigation and remains controversial.

Clinical Evidence of the Diagnostic and Prognostic Values of Eosinophils in IBD
An increased number of eosinophils have been found in the gut mucosa and luminal exudates in patients with IBD6–10 as compared with healthy individuals.11,12 Further studies have shown that exacerbations of ulcerative colitis (UC) are frequently accompanied by an increase in the number of circulating eosinophils and tissue eosinophilia,13 and an elevated eosinophil count may precede relapse.14 These eosinophils in the inflamed mucosa are largely degranulated on electronic microscopy.15

The diagnostic and prognostic roles of tissue eosinophilia in IBD are still debatable. Clinical investigations have been performed to assess association between eosinophil infiltration and disease activity. Sarin et al.16 showed rectal eosinophilic cell counts to be significantly higher in active UC than in quiescent UC and healthy controls, but there was no correlation between the eosinophil cell counts and disease severity. Jeziorska et al.17 reported an increased number of eosinophils only in active IBD, while much less in chronic quiescent disease. In contrast, Korelitz et al.18 described low mucosal eosinophil counts in active untreated UC. There was no correlation between the number of eosinophil in lamina propria and treatment response to sulfasalazine. The presence of tissue eosinophils corresponded to the general tendency for the condition to deteriorate and require intense medical therapy. Lampinen et al.19 further established that the activity of eosinophils was high in active disease. During this inactive phase of UC, patients had a higher number of eosinophils while being asymptomatic both clinically and histopathologically. These observations have sparked even more controversy, implying eosinophils might be involved also in the resolution of inflammation and repair of damaged tissue, which has also been elicited in allergy and asthma.20,21

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References:
  1. Seibold F,Weber P, Klein R, et al., Clinical significance of antibodies against neutrophils in patients with inflammatory bowel disease and primary sclerosing cholangitis, Gut, 1992;May 33(5):657–62.
  2. Fox CC, Lichtenstein LM, Roche JK, Intestinal mast cell responses in idiopathic inflammatory bowel disease. Histamine release from human intestinal mast cells in response to gut epithelial proteins, Dig Dis Sci, 1993;Jun 38(6):1105–12.
  3. Crowe SE, Perdue MH, Gastrointestinal food hypersensitivity: basic mechanisms of pathophysiology, Gastroenterology, 1992;Sep 103(3):1075–95.
  4. Rothenberg ME, Eosinophilia, N Engl J Med, 1998;May 28 338(22):1592–600.
  5. Filley WV, Holley KE, Kephart GM, et al., Identification by immunofluorescence of eosinophil granule major basic protein in lung tissues of patients with bronchial asthma, Lancet, 1982;Jul 3 2(8288):11–6.
  6. Truelove SC, Richards WCD, Biopsy Studies in ulcerative colitis, Br Med J, 1956;(1):1315–18.
  7. Lumb G, Protheroe RHB, Biopsy of the rectum in ulcerative colitis, Lancet, 1955;(2):1208–15.
  8. Goldgraber MB, Kirsner JB, Palmer WL, The histopathology of chronic ulcerative colitis and its pathogenic implications, Gastroenterology, 1960;(38) 596–604.
  9. Lumb G, Pathology of ulcerative colitis, Gastroenterology, 1961;(40): 290–8
  10. Antonisen P, Riis P, A new diagnostic approach to mucosal inflammation in protocolitis, Lancet, 1961;(2): 81–2.
  11. Bercovitz ZT, Sommers SC, Altered inflammatory reaction in nonspecific ulcerative colitis, Arch Intern Med, 1966;Apr;117(4):504–10.
  12. Binder V, Cell density in lamina propria of the colon. A quantitative method applied to normal subjects and ulcerative colitis patients, Scand J Gastroenterol, 1970;5(6):485–90.
  13. Wright R, Truelove SC, Circulating and tissue eosinophils in ulcerative colitis, Am J Dig Dis, 1966;Nov;11(11):831–46.
  14. Riisager PM, Eosinophil leukocytes in ulcerative colitis, Lancet, 1959;(2):1008.
  15. Ranlov P, Nielsen MH,Wanstrup J, Ultrastructure of the ileum in Crohn’s disease. Immune lesions and mastocytosis, Scand J Gastroenterol, 1972;7(5):471–6.
  16. Sarin SK, Malhotra V, Sen Gupta S, et al., Significance of eosinophil and mast cell counts in rectal mucosa in ulcerative colitis. A prospective controlled study, Dig Dis Sci, 1987;Apr; 32(4):363–7.
  17. Sarin SK, Malhotra V, Sen Gupta S, et al., Significance of eosinophil and mast cell counts in rectal mucosa in ulcerative colitis. A prospective controlled study, Dig Dis Sci, 1987;Apr; 32(4):363–7.
  18. Korelitz BI, Sommers SC, Responses to drug therapy in ulcerative colitis. Evaluation by rectal biopsy and mucosal cell counts, Am J Dig Dis, 1976 Jun;21(6):441–7.
  19. Lampinen M, Ronnblom A, Amin K, et al., Eosinophil granulocytes are activated during the remission phase of ulcerative colitis, Gut, 2005 Dec;54(12):1714–20.
  20. Phipps S, Ying S,Wangoo A, et al., The relationship between allergen-induced tissue eosinophilia and markers of repair and remodeling in human atopic skin, J Immunol, 2002 Oct;15;169(8):4,604–12.
  21. Flood-Page P, Menzies-Gow A, Phipps S, et al., Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics, J Clin Invest, 2003 Oct;112(7):1029–36.
  22. Heatley RV, James PD, Eosinophils in the rectal mucosa. A simple method of predicting the outcome of ulcerative proctocolitis?, Gut, 1979 Sep;20(9):787–91.
  23. Peterson CG, Eklund E, Taha Y, et al., 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 Jul;97(7):1755–62.
  24. Aydemir SA, Tekin IO, Numanoglu G, et al., Eosinophil infiltration, gastric juice and serum eosinophil cationic protein levels in Helicobacter pylori-associated chronic gastritis and gastric ulcer, Mediators Inflamm, 2004 Dec;13(5–6):369–72.
  25. Talley NJ, Kephart GM, McGovern TW, et al., Deposition of eosinophil granule major basic protein in eosinophilic gastroenteritis and celiac disease, Gastroenterology, 1992 Jul;103(1):137–45.
  26. Hallgren R, Colombel JF, Dahl R, et al., Neutrophil and eosinophil involvement of the small bowel in patients with celiac disease and Crohn’s disease: studies on the secretion rate and immunohistochemical localization of granulocyte granule constituents, Am J Med, 1989 Jan;86(1):56–64.
  27. Scott BB, Goodall A, Stephenson P, et al., Rectal mucosal plasma cells in inflammatory bowel disease, Gut, 1983 Jun;24(6):519–24.
  28. Heatley RV, James PD, Eosinophils in the rectal mucosa. A simple method of predicting the outcome of ulcerative proctocolitis?, Gut, 1979 Sep;20(9):787–91.
  29. Rosekrans PC, Meijer CJ, van der Wal AM, et al., Immunoglobulin containing cells in inflammatory bowel disease of the colon: a morphometric and immunohistochemical study, Gut, 1980 Nov;21(11):941
  30. Raab Y, Fredens K, Gerdin B, et al., Eosinophil activation in ulcerative colitis: studies on mucosal release and localization of eosinophil granule constituents, Dig Dis Sci, 1998 May;43(5):1061–70.
  31. Jeziorska M, Haboubi N, Schofield P, et al., Distribution and activation of eosinophils in inflammatory bowel disease using an improved immunohistochemical technique, J Pathol, 2001 Aug;194(4):484–92.
  32. Willoughby CP, Piris J, Truelove SC, Tissue eosinophils in ulcerative colitis, Scand J Gastroenterol, 1979;14(4):395–9.
  33. Takafuji S, Bischoff SC, De Weck AL, et al., IL-3 and IL-5 prime normal human eosinophils to produce leukotriene C4 in response to soluble agonists, J Immunol, 1991 Dec 1;147(11):3855–61.
  34. Sanderson CJ, Interleukin-5, eosinophils, and disease, Blood, 1992 Jun 15;79(12):3101–9.
  35. Lampinen M, Carlson M, Sangfelt P, et al., IL-5 and TNF-alpha participate in recruitment of eosinophils to intestinal mucosa in ulcerative colitis, Dig Dis Sci, 2001 Sep;46(9):2004–9.
  36. Carvalho AT, Elia CC, de Souza HS, et al., Immunohistochemical study of intestinal eosinophils in inflammatory bowel disease, J Clin Gastroenterol, 2003 Feb;36(2):120–25.
  37. Collins PD, Marleau S, Griffiths-Johnson DA, et al., Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo, J Exp Med, 1995 Oct 1;182(4):1169–74.
  38. Dubucquoi S, Janin A, Klein O, et al., Activated eosinophils and interleukin 5 expression in early recurrence of Crohn’s disease, Gut, 1995 Aug; 37(2):242–6.
  39. Foster PS, Hogan SP, Ramsay AJ, et al., Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model, J Exp Med, 1996 Jan 1;183(1):195–201.
  40. Matthews AN, Friend DS, Zimmermann N, et al., Eotaxin is required for the baseline level of tissue eosinophils, Proc Natl Acad Sci USA, 1998 May 26;95(11):6273–8.
  41. Mishra A, Hogan SP, Lee JJ, et al., Fundamental signals that regulate eosinophil homing to the gastrointestinal tract, J Clin Invest, 1999 Jun;103(12):1719–27.
  42. Garcia-Zepeda EA, Rothenberg ME, Ownbey RT, et al., Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia, Nat Med, 1996 Apr; 2(4):449–56.
  43. Ponath PD, Qin S, Ringler DJ, et al., Cloning of the human eosinophil chemoattractant, eotaxin. Expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils, J Clin Invest, 1996 Feb 1;97(3):604–12.
  44. Gerber BO, Zanni MP, Uguccioni M, et al., Functional expression of the eotaxin receptor CCR3 in T lymphocytes co-localizing with eosinophils, Curr Biol, 1997 Nov 1;7(11):836–43
  45. Tenscher K, Metzner B, Schopf E, et al., Recombinant human eotaxin induces oxygen radical production, Ca(2+)-mobilization, actin reorganization, and CD11b upregulation in human eosinophils via a pertussis toxin-sensitive heterotrimeric guanine nucleotide-binding protein, Blood, 1996 Oct 15;88(8):3,195–9.
  46. Chen W, Paulus B, Shu D, et al., Increased serum levels of eotaxin in patients with inflammatory bowel disease, Scand J Gastroenterol, 2001 May;36(5):515–20.
  47. Mir A, Minguez M, Tatay J, et al., Elevated serum eotaxin levels in patients with inflammatory bowel disease, Am J Gastroenterol, 2002 Jun;97(6):1452–7.
  48. Metcalfe DD, Mast cell mediators with emphasis on intestinal mast cells, Ann Allergy, 1984 Dec;53(6 Pt 2):563–75.
  49. Befus D, Goodacre R, Dyck N, et al., Mast cell heterogeneity in man. I. Histologic studies of the intestine, Int Arch Allergy Appl Immunol, 1985;76(3):232–6.
  50. Dvorak AM, Ultrastructural evidence for release of major basic protein-containing crystalline cores of eosinophil granules in vivo: cytotoxic potential in Crohn’s disease, J Immunol, 1980 Jul;125(1):460–62.
  51. Ackerman SJ, Loegering DA, Venge P, et al., Distinctive cationic proteins of the human eosinophil granule: major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin, J Immunol, 1983 Dec;131(6):2977–82.
  52. Gleich GJ, Adolphson CR, The eosinophilic leukocyte: structure and function, Adv Immunol, 1986;39:177–253.
  53. Venge P, Hakansson L, Peterson CG, Eosinophil activation in allergic disease, Int Arch Allergy Appl Immunol, 1987;82(3–4):333–7.
  54. Hallgren R, Terent A, Venge P, Eosinophil cationic protein (ECP) in the cerebrospinal fluid, J Neurol Sci, 1983 Jan;58(1):57–71.
  55. Hallgren R, Bjelle A, Venge P, Eosinophil cationic protein in inflammatory synovial effusions as evidence of eosinophil involvement, Ann Rheum Dis, 1984 Aug;43(4):556–62.
  56. Saitoh O, Kojima K, Sugi K, et al., Fecal eosinophil granule-derived proteins reflect disease activity in inflammatory bowel disease, Am J Gastroenterol, 1999 Dec;94(12):3513–20.
  57. Berstad A, Börke B, Riedel B, et al., Increased fecal eosinophil cationic protein in inflammatory bowel disease, Hepatogastroenterology, 1993;40:276–8.
  58. Bischoff SC, Grabowsky J, Manns MP, Quantification of inflammatory mediators in stool samples of patients with inflammatory bowel disorders and controls, Dig Dis Sci, 1997;42:394–403.
  59. Sangfelt P, Carlson M, Thorn M, et al., Neutrophil and eosinophil granule proteins as markers of response to local prednisolone treatment in distal ulcerative colitis and proctitis, Am J Gastroenterol, 2001;96:1085–90.
  60. Levy AM, Gleich GJ, Sandborn WJ, et al., Increased eosinophil granule proteins in gut lavage fluid from patients with inflammatory bowel disease, Mayo Clin Proc, 1997;72:117–23.
  61. Kristjansson G, Venge P,Wanders A, et al., 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 Dec;53(12):1,806–12.
  62. D’Arienzo A, Manguso F, Astarita C, et al., Allergy and mucosal eosinophil infiltrate in ulcerative colitis, Scand J Gastroenterol, 2000 Jun;35(6):624–31.
  63. Ceyhan BB, Karakurt S, Cevik H, et al., Bronchial hyperreactivity and allergic status in inflammatory bowel disease, Respiration, 2003 Jan–Feb;70(1):60–6.
  64. Louis E, Louis R, Shute J, et al., Bronchial eosinophilic infiltration in Crohn’s disease in the absence of pulmonary disease, Clin Exp Allergy, 1999 May;29(5):660–6.
  65. Levo Y, Shalit M,Wollner S, et al., Serum IgE levels in patients with inflammatory bowel disease, Ann Allergy, 1986 Jan;56(1):85–7.
  66. Taylor KB, Truelove SC, Circulating antibodies to milk proteins in ulcerative colitis, Br Med J, 1961 Oct 7;2(5257):924–9.
  67. Andresen AFR, Gastrointestinal manifestations of food allergy, J Med Res, 1925;122:171–5
  68. Wright R, Truelove SR, Serial rectal biopsy in ulcerative colitis during the course of a controlled therapeutic trial of various diets, Am J Dig Dis, 1966 Nov;11(11):847–57.
  69. Taylor KB, Truelove SC, Wright R, Serologic reactions to gluten and cow’s milk proteins in Gastrointestinal Disease, Gastroenterology, 1964 Feb;46:99–108.
  70. Falchuk KR, Isselbacher KJ, Circulating antibodies to bovine albumin in ulcerative colitis and Crohn’s disease. Characterization of the antibody response, Gastroenterology, 1976 Jan;70(1):5–8.
  71. Jewell DP, Truelove SC, Circulating antibodies to cow’s milk proteins in ulcerative colitis, Gut, 1972 Oct;13(10):796–801.
  72. Glassman MS, Newman LJ, Berezin S, et al., Cow’s milk protein sensitivity during infancy in patients with inflammatory bowel disease, Am J Gastroenterol, 1990 Jul; 85(7):838–40.
  73. Binder JH, Gryboski JD, Thayer WR Jr, et al., Intolerance to milk in ulcerative colitis. A preliminary report, Am J Dig Dis, 1966 Nov;11(11):858–64.
  74. Mishkin S, Dairy sensitivity, lactose malabsorption, and elimination diets in inflammatory bowel disease, Am J Clin Nutr, 1997 Feb;65(2):564–7.
  75. Cashman KD, Shanahan F, Is nutrition an aetiological factor for inflammatory bowel disease?, Eur J Gastroenterol Hepatol, 2003 Jun;15(6):607–13.
  76. Rothenberg ME, Eosinophilic gastrointestinal disorders (EGID), J Allergy Clin Immunol, 2004 Jan;113(1):11–28.
  77. Stellato C, Matsukura S, Fal A, et al., Differential regulation of epithelial-derived C-C chemokine expression by IL-4 and the glucocorticoid budesonide, J Immunol, 1999 Nov 15;163(10):5624–32.
  78. Schleimer RP, Bochner BS, The effects of glucocorticoids on human eosinophils, J Allergy Clin Immunol, 1994 Dec;94(6 Pt 2):1202–13.
  79. Barnes PJ, Adcock IM, Steroid resistance in asthma, QJM, 1995 Jul;88(7):455–68.
  80. Aldebert D, Lamkhioued B, Desaint C, et al., Eosinophils express a functional receptor for interferon alpha: inhibitory role of interferon alpha on the release of mediators, Blood, 1996 Mar 15;87(6):2354–60.
  81. Morley J, Cyclosporin A in asthma therapy: a pharmacological rationale, J Autoimmun, 1992 Apr;5 Suppl A:265–9.
  82. Okada S, Hagan JB, Kato M, et al., Lidocaine and its analogues inhibit IL-5-mediated survival and activation of human eosinophils, J Immunol, 1998 Apr 15;160(8):4010–17.
  83. Bankers-Fulbright JL, Kephart GM, Loegering DA, et al., Sulfonylureas inhibit cytokine-induced eosinophil survival and activation, J Immunol, 1998 Jun 1;160(11):5546–53.
  84. Mauser PJ, Pitman AM, Fernandez X, et al., Effects of an antibody to interleukin-5 in a monkey model of asthma, Am J Respir Crit Care Med, 1995 Aug;152(2):467–72.
  85. Egan RW, Athwahl D, Chou CC, et al., Inhibition of pulmonary eosinophilia and hyperreactivity by antibodies to interleukin-5, Int Arch Allergy Immunol, 1995 May–Jun;107(1–3):321–2.
  86. Zimmermann N, Hershey GK, Foster PS, et al., Chemokines in asthma: cooperative interaction between chemokines and IL-13, J Allergy Clin Immunol, 2003 Feb;111(2):227–42.
  87. Snyman JR, Sommers DK, Gregorowski MD, et al., Effect of cetirizine, ketotifen and chlorpheniramine on the dynamics of the cutaneous hypersensitivity reaction: a comparative study, Eur J Clin Pharmacol, 1992;42:359–362.
  88. Redier H, Chanez P, De Vos C, et al., Inhibitory effect of cetirizine on the bronchial eosinophil recruitment induced by allergen inhalation challenge in allergic patients with asthma, J Allergy Clin Immunol, 1992;90:215–24.
  89. Rand TH, Lopez AF, Gamble JR, et al., Nedocromil sodium and cromolyn (sodium cromoglycate) selectively inhibit antibodydependent granulocyte-mediated cytotoxicity, Int Arch Allergy Appl Immunol, 1988;87:151–158.
  90. Rampton DS, Brown MJ, Causon R, et al., The effect of disodium cromoglycate on rectal mucosal histamine release, eosinophil exudation and disease activity in active ulcerative colitis, Clin Allergy, 1982 May;12(3):243–8.
  91. Jones NL, Roifman CM, Griffiths AM, et al., Ketotifen therapy for acute ulcerative colitis in children: a pilot study, Dig Dis Sci, 1998 Mar;43(3):609–15.

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