Leukotriene B4 and C4 metabolism in small intestine mucosa of children with celiac disease.

The enhanced generation of eicosanoids, including leukotrienes (LTs), may be involved in the pathophysiology of small intestine mucosal injury in patients with celiac disease. We investigated the metabolism of LTB4 and LTC4 by small intestine mucosa in patients with celiac disease by incubating biopsies of small intestine mucosa from patients and healthy subjects in media containing LTB4 and LTC4 and measuring the changes in LTB4 and cysteinyl LT concentrations in the incubation media. There was no significant degradation of LTB4 during a 60-min incubation of the small intestine mucosa from either children with celiac disease or controls. LTC4 was metabolized to LTD4 and LTE4 in a time-dependent manner by the small intestine mucosa of both patients and controls. However, the decreases in LTC4 and the increases in LTD4 and LTE4 by the intestinal mucosa from patients with celiac disease occurred more slowly than the changes observed in control experiments. Reduced catabolism of LTC4 in the small intestine mucosa due to villous atrophy may contribute to increased levels of LTC4 and may play an important role in the pathophysiology of celiac disease.