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HOME > Kosin Med J > Volume 28(2); 2013 > Article
Original Article Preventive and Therapeutic Effects of Anisakis simplex Larval Protein in a Mouse Model of Crohn’S Disease
Hee-Jae Cha, Mee Sun Ock
Kosin Medical Journal 2013;28(2):107-113.
DOI: https://doi.org/10.7180/kmj.2013.28.2.107
Published online: January 19, 2013
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Department of Parasitology and Genetics, College of Medicine, Kosin University, Busan, Korea

Corresponding author: Mee Sun Ock, Department of Parasitology and Genetics, College of Medicine, Kosin University, 262 Kamchunro Seogu, Busan, 602-703, Korea TEL: +82-51-990-6424 FAX: +82-51-990-3081 E-mail: sunnyock@kosin.ac.kr
• Received: March 7, 2013   • Accepted: April 24, 2013

Copyright © 2013 Kosin University School of Medicine Proceedings

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • Objectives
    Some helminths have been known to have a treatment effect in inflammatory bowel diseases, including Crohn’s disease (CD); however, live parasite therapy can cause unwanted side effects. To develop a safe therapeutic, we investigated the preventive or therapeutic potential of proteins from the third stage larva of A. simplex in a mouse model. We also analyzed the cytokine profile from splenic and mesenteric lymph node lymphocytes to elucidate the underlying immunological mechanism.
  • Methods
    CD was induced in mice with DSS, and the effect of an A. simplex larval protein on CD was assessed. A change in body weight and DAI (disease activity index) were observed in mice. The expression levels of cytokines from mesenteric lymph nodes (MLN) compared to splenic lymphocytes were measured with ELISA.
  • Results
    Peritoneal administration of preventive and therapeutic A. simplex larval proteins attenuated DSS-induced CD by a reduction of the DAI and weight loss. A shortening of colon length was more definitely observed in the therapeutic group than in the preventive group. The cytokine expression levels were more obvious in lymphocytes from mesenteric lymph nodes than from splenic lymphocytes.
  • Conclusions
    Taken together, these results suggest that A. simplex proteins can change cytokine profiles and may have a preventive effect in DSS-induced CD mice.
Fig. 1.
Changes in body weight in each group of mice. SP + DSS and ES + DSS groups are preventive groups; DSS + SP and DSS + ES groups are therapeutic groups. The average body weight was higher in the preventive groups than in the therapeutic groups.
kmj-28-107f1.jpg
Fig. 2.
DAI’s were measured daily during the experimental period in each group of mice. SP + DSS and ES + DSS groups are preventive groups; DSS + SP and DSS + ES group are therapeutic groups.
kmj-28-107f2.jpg
Fig. 3.
The representative colon from each group of mice. (C) control group, (D) DSS-treated group, (A) preventive group, (B) therapeutic group. The colons of the mice in the preventive group maintained their original length.
kmj-28-107f3.jpg
Fig. 4.
Cytokine profile of splenic and lymph node lymphocytes. Expression levels of IL-α (A), IL-1β (B), IL-2 (C), and IFN-γ (D) were measured with ELISA after administration of A. simplex protein. C; control, DSS; DSS only, Asp and Aes denotes preventive group injected with SP (somatic protein) and ES (excretory-secretory) protein.
kmj-28-107f4.jpg
  • 1.Strachan DP. Hay fever, hygiene, and household size. BMJ 1989;299:1259–60.ArticlePubMedPMC
  • 2.Yazdanbakhsh M, Kremsner PG, van Ree R. Allergy, parasites, and the hygiene hypothesis. Science. 2002;296:490–4.ArticlePubMed
  • 3.Weinstock JV, Elliott DE. Helminths and the IBD hygiene hypothesis. Inflamm Bowel Dis 2009;15:128–33.ArticlePubMed
  • 4.Summers RW, Elliott DE, Urban JF Jr, Thompson RA, Weinstock JV. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 2005;128:825–32.ArticlePubMed
  • 5.Mortimer K, Brown A, Feary J, Jagger C, Lewis S, Antoniak M, et al. Dose-ranging study for trials of therapeutic infection with Necator americanus in humans. Am J Trop Med Hyg 2006;75:914–20.ArticlePubMed
  • 6.Van Kruiningen HJ, West AB. Potential danger in the medical use of Trichuris suis for the treatment of inflammatory bowel disease. Inflamm Bowel Dis 2005;11:515.Article
  • 7.Hsu S-J, Tseng P-H, Chen P-J. Trichuris suis therapy for ulcerative colitis: nonresponsive patients may need anti-helminth therapy. Gastroenterology 2005;129:768–9.ArticlePubMed
  • 8.Cho MK, Ahn SC, Kim DH, Yu HS. Parasite excretory-secretory proteins elicit TRIF dependent CXCL1 and IL-6 mediated allergic inflammation. Parasite Immunol 2010;32:354–60.ArticlePubMed
  • 9.Park SK, Cho MK, Park HK, Lee KH, Lee SJ, Choi SH, et al. Macrophage migration inhibitory factor homologs of Anisakis simplex suppress Th2 response in allergic airway inflammation model via CD4+CD25+Foxp3+ T cell recruitment. J Immunol 2009;182:6907–14.ArticlePubMed
  • 10.Kim J, Jo JO, Choi SH, Cho MK, Yu HS, Cha HJ, et al. Seroprevalence of antibodies against Anisakis simplex larvae among health-examined residents in three hospitals of southern parts of Korea. Korean J Parasitol 2011;49:139–44.ArticlePubMedPMC
  • 11.Breese E, Braegger CP, Corrigan CJ, Walker-Smith JA, MacDonald TT. Interleukin-2- and interferon-gamma-secreting T cells in normal and diseased human intestinal mucosa. Immunology 1993;78:127–31.PubMedPMC
  • 12.Fuss IJ, Neurath M, Boirivant M, Klein JS, de la Motte C, Strong SA, et al. Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn's disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol 1996;157:1261–70.PubMed
  • 13.Hommes DW, Mikhajlova TL, Stoinov S, Stimac D, Vucelic B, Lonovics J, et al. Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn's disease. Gut 2006;55:1131–7.ArticlePubMedPMC
  • 14.Reinisch W, Hommes DW, Van Assche G, Colombel JF, Gendre JP, Oldenburg B, et al. A dose escalating, placebo controlled, double blind, single dose and multidose, safety and tolerability study of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease. Gut 2006;55:1138–44.ArticlePubMedPMC
  • 15.Ruyssers NE, De Winter BY, De Man JG, Loukas A, Pearson MS, Weinstock JV, et al. Therapeutic potential of helminth soluble proteins in TNBS-induced colitis in mice. Inflamm Bowel Dis 2009;15:491–500.ArticlePubMed
  • 16.Summers RW, Elliott DE, Urban JF Jr, Thompson R, Weinstock JV. Trichuris suis therapy in Crohn's disease. Gut 2005;54:87–90.ArticlePubMedPMC
  • 17.Khan WI, Blennerhasset PA, Varghese AK, Chowdhury SK, Omsted P, Deng Y, et al. Intestinal nematode infection ameliorates experimental colitis in mice. Infect Immun 2002;70:5931–7.ArticlePubMedPMC

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