title: Hookworm products ameliorate dextran sodium sulfate-induced colitis in BALB/c mice.
abstract: BACKGROUND
  Several lines of evidence have shown that helminthiasis can significantly reduce disease severity in animal models of intestinal inflammation, airway inflammation/hyperreactivity, diabetes, and multiple sclerosis. Identification and characterization of helminth-derived immunomodulatory molecules that contribute to anticolitis effects could lead to new therapeutic approaches in inflammatory bowel diseases (IBDs) without the need for helminth infection. We evaluated the therapeutic potential of adult human hookworm, Ancylostoma ceylanicum, crude (Aw) and excreted/secreted (ES) products on dextran sulfate sodium (DSS)-induced colitis in BALB/c mice.
  
  
  METHODS
  Colitis was induced by 5% DSS oral administration for 7 days. Clinical disease severity was monitored daily during concomitant intraperitoneal treatment with helminth-derived products. Additionally, several pathways of immunological modulation induced by A. ceylanicum products (MPO, EPO, Th1, Th2, and Th17 cytokine responses) in the inflamed intestinal microenvironment were assessed. Finally, the histopathological profile of the colon was characterized.
  
  
  RESULTS
  Hookworm products are able to modulate the potent proinflammatory response induced by DSS, mainly through the downregulation of Th1 and Th17 cytokines. These proteins also reduce clinical and colonic microscopic inflammation scores as well as EPO and MPO activity.
  
  
  CONCLUSIONS
  Ancylostoma ceylanicum Aw and ES mediators have an important therapeutic potential in experimental colitis in mice, which may provide a more socially acceptable form of therapy for patients with IBDs as opposed to using living worms. Our results support the urgency of further isolation and recombinant expression of active hookworm products responsible for the beneficial effects on colitis.
authors.affiliation: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil. guilhermegrossi@terra.com.br
authors.forename: Guilherme Grossi Lopes
authors.initials: GG
authors.lastname: Cançado
authors.forename: Jacqueline Araújo
authors.initials: JA
authors.lastname: Fiuza
authors.forename: Nivia Carolina Nogueira
authors.initials: NC
authors.lastname: de Paiva
authors.forename: Lucas de Carvalho Dhom
authors.initials: Lde C
authors.lastname: Lemos
authors.forename: Natasha Delaqua
authors.initials: ND
authors.lastname: Ricci
authors.forename: Pedro Henrique
authors.initials: PH
authors.lastname: Gazzinelli-Guimarães
authors.forename: Virgillio Gandra
authors.initials: VG
authors.lastname: Martins
authors.forename: Daniella Castanheira
authors.initials: DC
authors.lastname: Bartholomeu
authors.forename: Deborah Aparecida
authors.initials: DA
authors.lastname: Negrão-Corrêa
authors.forename: Cláudia Martins
authors.initials: CM
authors.lastname: Carneiro
authors.forename: Ricardo Toshio
authors.initials: RT
authors.lastname: Fujiwara
mesh_terms: D000328:Adult; D000722:Ancylostoma / Q000502:physiology*; D000724:Ancylostomiasis; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity*; D004195:Disease Models, Animal; D015801:Helminth Proteins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000378:metabolism
chemical_list: D016207:Cytokines; D015801:Helminth Proteins; D016264:Dextran Sulfate; D009195:Peroxidase