Hookworm products ameliorate dextran sodium sulfate-induced colitis in BALB/c mice

GGL Cançado, JA Fiuza, NCN de Paiva… - Inflammatory bowel …, 2011 - academic.oup.com
GGL Cançado, JA Fiuza, NCN de Paiva, L de Carvalho Dhom Lemos, ND Ricci…
Inflammatory bowel diseases, 2011academic.oup.com
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 …
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. (Inflamm Bowel Dis 201117:2275–2286)
Oxford University Press