Abstract
Increased ileal permeability may play a role in the pathogenesis of Crohn's disease (CD). fMLP, a common bacterial peptide, initiates inflammation and increased permeability in the rat ileum via neutrophil activation and chemotaxis. We investigated the effect of 6MP often used to treat CD, upon fMLP-induced changes in ileal macromolecular uptake. METHODS: Using in situ ileal perfusion, permeability to 0.5%. horseradish peroxidase (HRP), ± simultaneous luminal perfusion of 10 −5M fMLP, was measured by blood levels over 90 min, in each of 3 groups of male rats: Group I = daily 48 mg 6MP m−2 for 14 days; Group II = vehicle-injected, pair fed controls; Group III = ad libitum controls. RESULTS: In the absence of fMLP, HRP uptake was low in all Groups (90 min blood HRP <37 ± 5 units)(mean ± SE). With fMLP, HRP uptake was markedly elevated over basal in rats not receiving CMP: Group II = 210 ± 12; Group III = 263 ± 24 units, (p<0.01). Conversely, 6MP treatment (Group I) ameliorated the fMLP response (106 ± 8 units, p<0.01). 6MP therapy decreased the circulating neutrophil count, but did not alter mucosal myeloperoxidase, a neutrophil marker. CONCLUSION: 6MP therapy decreases macromolecular uptake induced by fMLP. SPECULATION: In CD, CMP may be therapeutic through diminished neutrophil inflammatory response and reduced antigen uptake.
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