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031 - CCFC STUDENT PRIZE

TAPEWORM EXAGGERATION OF TH2 COLITIS: INVOLVEMENT OF INTERLEUKIN-5

MM Hunter¹, DM McKay^2
1Intestinal Disease Research Programme, McMaster University; ²Gastrointestinal Research Group, University of Calgary

We have shown that infection with the rat tapeworm Hymenolepis diminuta reduces the severity of DNBS-induced colitis (TH1-type) but increases the inflammation associated with oxazolone-induced colitis (TH2-type). One of the histopathological features that separates these colitidies is the presence of eosinophils in oxazolone-induced disease. Since infection with parasitic helminths also results in an eosinophil response we reasoned that this could underly H. diminuta enhancement of oxazolone-induced colitis: the helminth-driven eosinophil response is dependent of the mobilization of IL-5. Here we assessed the impact of a replication-deficient adenovirus engineered to encode the IL-5 gene (Ad-IL-5) in the oxazolone model of colitis. Male Balb/c mice received an injection of Ad-IL-5 (10⁹ pfu/100µl PBS) followed 24 hours later by intra-rectal oxazolone (ox; 3mg in 50% EtOH). Mice were assessed 3 days post-oxazolone, at which time colon length was recorded and portions of the colon processed for measurement of myeloperoxidase and eosinophil peroxidase activity. Mice that received oxazolone-only showed signs of colitis and this was significantly enhanced by co-treatment with Ad-IL-5 (Table). Ad-IL-5 infection was also associated with increased eosinophil peroxidase activity in the colon.
                                                 

Treatment	body weight	clinical score	colon length (mm)	MPO activity
Control	0.2 ± 0 .1	0 ± 0	108 ± 1.7	0.31 ± 0.06
Add/Delete	0.2 ± 0.1	0 ± 0	104 ± 1.3	0.36 ± 0.07
Ad-IL-5	0.2 ± 0.1	0 ± 0	103 ± 1.5	0.34 ± 0.05
Oxazolone	-0.7 ± 0.3	1 ± 0.3	94 ± 2.6	1.26 ± 0.36
Ox + Ad-IL-5	-2.0 ± 0.6 *	2.5 ± 0.5 *	84 ± 3.3 *	2.70 ± 0.54 *
Ox+ Add/Del a	-1.1 ± 0.1	1.2 ± 0.1	92 ± 1.7	1.42 ± 0.02

 (mean ± SEM; *, p<0.05; a, n=3, all other groups n=12)
These results demonstrate that IL-5 potentiates the effect of oxazolone colitis leading a much more severe disease that is mediated, at least in part, by mobilization of an eosinophil response. Thus, in considering helminth therapy to treat IBD, we suggest that this would be counter-indicated in individuals with elevated local or system eosinophils.
Funded by the CCFC

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