Prostaglandin E2 in jejunal fluids and its potential diagnostic value for selecting patients with indomethacin-sensitive diarrhoea

Abstract

Since prostaglandins (PGs) appear to be important in the pathogenesis of secretory diarrhoea, a radioimmunoassay for determination of PGE2 was applied to purified samples of jejunal fluids aspirated at the ligament of Treitz. Studies on validation of the assay system included quantification of PGE2 following alkali-treatment of the samples, variation of the sample volume, and fractionation of immunoreactive- and tracer PGE2. In addition, the specificity of the assay system was confirmed by gas chromatography--mass spectrometry. In healthy volunteers (n = 22) the PGE2 concentration range was 5--205 pg/ml (99% confidence limits). Alcohol addicts (n = 27) with diarrhoea or steatorrhoea had PGE2 levels within the normal range. Values beyond the 99% upper confidence limit were observed in ten out of seventeen patients with chronic diarrhoea (205--340 pg/ml) and two out of fifteen patients with intermittent diarrhoea (265 and 275 pg/ml) classified as irritable bowel syndrome. In six patients with high PGE2 concentrations indomethacin treatment (25 mg x 4 daily) halved the associated diarrhoea and reduced PGE2 concentrations to normal levels. Subsequently, a double-blind multiple randomized clinical trial was carried out in two single patients. Indomethacin proved to be effective in preventing diarrhoea only in the patient with a raised PGE2 level (P less than 0.005).