CCFC STUDENT PRIZE WINNER
TAPEWORM INFECTION REDUCES INFLAMMATION IN A MURINE MODEL OF COLITIS

MM Hunter, A Wang, RA Webb¹, & DM McKay

Intestinal Disease Research Program, McMaster University, Hamilton, Ontario, and ¹Biology Department, York University, Toronto, Ontario

T helper cells can be divided into TH1 and TH2 subtypes, with representative cytokines from each cell exerting an inhibitory function on the reciprocal helper T cell. The human inflammatory bowel disease, Crohn's disease, is associated with an increase in TH1 cytokines, while parasitic helminthes are strong inducers of TH2 responses. Thus, the postulate arises that helminth infection could prevent or reduce TH1 dominated inflammation, e.g. Crohn's disease. To test this we employed the rat tapeworm Hymenolepis diminuta, which is spontaneously expelled from mice, and the DNBS model of murine colitis. Male BALB/c mice received 5 infective larvae of H. diminuta and 10 days later colitis was evoked by intra-rectal DNBS (3mg) instillation in 50% ethanol. Mice were examined daily and a clinical score calculated 72h post-DNBS. On autopsy, colon length was measured and portions of the colon were fixed for histological examination and MPO determinations. Controls consisted of naïve and ethanol only treated mice. As expected, mice that only received DNBS developed wasting and obvious macroscopic and microscopic signs of colitis. However, mice infected with H. diminuta were significantly protected from the DNBS colitis.

These data demonstrate that infection with H. diminuta prior to the onset of chemically-induced TH1-type colitis reduces the severity of the disease, and represents a proof-of-principal evidence in support of the stated hypothesis. We speculate that precise analysis of patients with Crohn's disease may identify some individuals for which "helminth therapy", or immune deviation, would be an effective anti-inflammatory strategy.

This work was supported by grants from CIHR and CCFC.