leukotriene-c4 and Celiac-Disease

The pathophysiology of intestinal inflammation and diarrhoea is complex and involves the arachidonic acid cascade. Prostaglandins induce chloride secretion in healthy subjects and in patients with coeliac disease. Leukotrienes (LTs) are also known inflammatory mediators which have been shown to stimulate ion secretion in ileum and colon of rats and rabbits. The aim of this study was to determine the effects of leukotrienes C(4) (LTC(4)) and D(4) (LTD(4)) in normal and atrophic intestinal mucosa in children.. Routine paediatric intestinal biopsies were obtained from 109 children. Sixty-seven control biopsies and 42 biopsies from children with different stages of coeliac disease were mounted in a modified Ussing chamber. Potential difference (Pd) was measured continuously and tissue resistance (R(t)) and the generated current (I(m)) were calculated.. In morphologically normal mucosa of duodenum, LTC(4) and LTD(4) increased Pd and I(m) in a dose-dependent manner. The increase was more pronounced in the distal than in the proximal part, similar to the response to prostaglandin E(2). The induced current was chloride-mediated, since replacement of Cl(-) with SO(4)(2-) in the bathing solution eliminated the response to the LTs. The LTC(4)-induced secretion was significantly decreased in atrophic mucosa, but the response was partially restored after preincubation with the cyclooxygenase inhibitor indomethacin.. The results showed that LTC(4) and LTD(4) are secretagogues in the duodenal mucosa from healthy children by inducing a net chloride secretion. Restoration of the response in coeliac disease by cyclooxygenase inhibition suggests interactions between the different pathways of the arachidonic cascade in the intestinal mucosa.

Topics: Atrophy; Celiac Disease; Child; Child, Preschool; Cysteine; Duodenum; Humans; Infant; Intestinal Mucosa; Intestines; Leukotriene C4; Leukotriene D4; Leukotrienes; Lipoxygenase; Prostaglandin-Endoperoxide Synthases

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.

Topics: Biopsy; Celiac Disease; Child, Preschool; Humans; In Vitro Techniques; Infant; Intestinal Mucosa; Intestine, Small; Kinetics; Leukotriene B4; Leukotriene C4

The capacity of the small intestinal mucosa to generate leukotriene B4 (LTB4) and C4 (LTC4) in children with coeliac disease (CD) was investigated by measuring the production of LTB4 and LTC4 in intestinal biopsy specimens after stimulation with 10 microM calcium ionophore A23187. In addition, we examined the relationship between the production of LTB4 and LTC4 in the small intestinal mucosa and symptoms of diarrhoea. LTB4 and LTC4 production was significantly higher in biopsies from patients with active CD than from controls (p < 0.05 and p < 0.01, respectively). There was no significant difference in LTB4 and LTC4 production between patients with inactive CD and controls. In both patients with active CD and controls, no difference in LTB4 and LTC4 production was observed between the patients with and without diarrhoea. These findings suggest that enhanced generation of LTB4 and LTC4 in the small intestinal mucosa may contribute to the pathophysiology of CD but would not be related to the development of diarrhoea.

Topics: Calcimycin; Celiac Disease; Child; Child, Preschool; Data Interpretation, Statistical; Diarrhea; Humans; In Vitro Techniques; Infant; Intestinal Mucosa; Intestine, Small; Leukotriene B4; Leukotriene C4; Radioimmunoassay