Objective. The pathophysiology of intestinal inflammation and diarrhoea is co mplex and involves the arachidonic acid cascade. Prostaglandins induce chloride secretion in healthy subjects and in patients with coeliac ...Objective. The pathophysiology of intestinal inflammation and diarrhoea is co mplex 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 (LTC 4) 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 biop sies and 42 biopsies from children with different stages of coeliac disease were mounted in a modified Ussing chamber. Potential difference (Pd) was measured co ntinuously and tissue resistance (Rt) and the generated current (Im) were calcul ated. Results. In morphologically normal mucosa of duodenum, LTC4 and LTD4 incre ased Pd and Im 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 respon se was partially restored after preincubation with the cyclooxygenase inhibitor indomethacin. Conclusions. The results showed that LTC4 and LTD4 are secretagogu es in the duodenalmucosa from healthy children by inducing a net chloride secret ion. Restoration of the response in coeliac disease by cyclooxygenase inhibition suggests interactions between the different pathways of the arachidonic cascade in the intestinal mucosa.展开更多
文摘Objective. The pathophysiology of intestinal inflammation and diarrhoea is co mplex 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 (LTC 4) 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 biop sies and 42 biopsies from children with different stages of coeliac disease were mounted in a modified Ussing chamber. Potential difference (Pd) was measured co ntinuously and tissue resistance (Rt) and the generated current (Im) were calcul ated. Results. In morphologically normal mucosa of duodenum, LTC4 and LTD4 incre ased Pd and Im 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 respon se was partially restored after preincubation with the cyclooxygenase inhibitor indomethacin. Conclusions. The results showed that LTC4 and LTD4 are secretagogu es in the duodenalmucosa from healthy children by inducing a net chloride secret ion. Restoration of the response in coeliac disease by cyclooxygenase inhibition suggests interactions between the different pathways of the arachidonic cascade in the intestinal mucosa.
