Cysteinyl leukotrienes are secretagogues in atrophic coeliac and in normal duodenal mucosa of children

Abstract

Objective 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 C₄ (LTC₄) and D₄ (LTD₄) in normal and atrophic intestinal mucosa in children.

Material and methods 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.

Results In morphologically normal mucosa of duodenum, LTC₄ and LTD₄ 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 E₂. The induced current was chloride-mediated, since replacement of Cl⁻ with SO₄²⁻ in the bathing solution eliminated the response to the LTs. The LTC₄-induced secretion was significantly decreased in atrophic mucosa, but the response was partially restored after preincubation with the cyclooxygenase inhibitor indomethacin.

Conclusions The results showed that LTC₄ and LTD₄ 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.

• Coeliac disease
• human intestine
• ion transport
• leukotriene
• secretion