leukotriene-b4 and 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.

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

Celiac disease (CD) is characterized by diarrhea, growth retardation, and weight loss in genetically susceptible subjects on a gluten-containing diet. The exact pathogenesis of CD is still obscure, but it is considered to be immunologically mediated. We have previously shown elevated prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) content in small intestinal mucosa obtained from active celiac children. In the present study, we found significantly elevated PGE2, leukotriene B4 (LTB4), and leukotrienes C4, D4, and E4 (LTC4D4E4) content in small bowel mucosa from children suffering from CD on a gluten-containing diet in comparison to control subjects. PGE2 was 25,278 +/- 7,761 vs. 4,478 +/- 426 pg/mg of protein (mean +/- SEM), respectively. LTB4 was 8,807 +/- 3,706 vs. 403 +/- 63 pg/mg of protein (mean +/- SEM), respectively. LTC4D4E4 was 15,369 +/- 4,085 vs. 2,998 +/- 279 pg/mg of protein (mean +/- SEM), respectively. We conclude that the elevated content of arachidonic acid metabolic products via cyclooxygenase and lipoxygenase pathways may contribute to the diarrhea and may be involved in the pathogenesis of mucosal injury.

Topics: Adolescent; Celiac Disease; Child; Child, Preschool; Dinoprostone; Eicosanoids; Humans; Infant; Intestinal Mucosa; Intestine, Small; Leukotriene B4; SRS-A

Topics: Calcimycin; Celiac Disease; Child; Child, Preschool; Humans; Intestinal Mucosa; Intestine, Small; Leukotriene B4; SRS-A