Short-chain (C2-C6) fatty acids (SCFA) are the major anions in colonic contents and the result of anaerobic fermentation of mainly saccharides. The effects and regulation of saccharide fermentation were studied in vitro and in vivo. In vitro faecal incubation was used to study the effects of lactose, glucose, and galactose and of pH on SCFA formation. Changing the pH to below 5 or above 11 abolished SCFA formation in the faecal incubates; in the pH 5-9 interval SCFA production was high, with only minor pH dependence. Adding glucose, galactose, or lactose to the incubation system increased SCFA production, but at high saccharide concentrations (100-300 mmol/l) SCFA formation was inhibited by the pH change. In vivo disaccharide malabsorption with increasing doses of lactulose caused a decrease in faecal pH to less than 5, values inhibitory to fermentation, before the appearance of carbohydrate in faeces. In 6 of 12 volunteers diarrhoea occurred suddenly and was caused by malabsorbed non-fermented carbohydrate. The six other volunteers had a gradual increase in faecal output with lactulose dose and developed diarrhoea before the appearance of saccharide in faeces. The intake of lactulose tolerated before diarrhoea ensued varied between individuals, with the majority having diarrhoea of more than 11/day at 160 g lactulose per day. At this dose SCFA absorption was estimated to be in the range 550 to 1150 mmol/day.

In this report a method for the affinity purification and radiolabeling of recombinant mouse interleukin (IL)-4 is described. It is shown on the basis of several criteria that IL-4 retains full biologic activity after radioiodination and can therefore be used as a valid model for measuring the binding characteristics of native IL-4. By using Scatchard plot analysis of equilibrium binding data, it is demonstrated that 125I-IL-4 binds to a high affinity cell surface receptor which is expressed by both hemopoietic and nonhemopoietic cells. The dissociation constant for 125I-IL-4 (Kd = 20 to 60 pM) corresponds to the concentration of IL-4 which gives 50% biologic activity (i.e., 10 to 30 pM). Binding of 125I-IL-4 is rapid (t1/2 of 2 min), whereas dissociation occurs at a slow rate (t1/2 approximately 4 hr). The IL-4 receptor shows a high degree of specificity. Whereas unlabeled mouse IL-4 competed with mouse 125I-IL-4 in an equimolar fashion for binding to IL-4 receptors, several other lymphokines, including mouse IL-2, IL-3, interferon-gamma, granulocyte-macrophage colony-stimulating factor, and human IL-1, IL-2, and IL-4 were unable to inhibit, even at molar excesses of 400 to 800-fold. At 37 degrees C, 125I-IL-4 is rapidly internalized (approximately 200 molecules/cell/min) by HT-2 cells, with at least 85% of cell surface receptors being functional in this respect. Receptors for IL-4 were found to be expressed by subclasses of T and B cells, mast cells, macrophages, and by cells of the myeloid and erythroid lineages. This wide distribution of receptor expression closely matches the known spectrum of biologic activities of IL-4, including proliferation and/or differentiation of T and B cells, mast cells and granulocytes, and induction of macrophage antigen-presenting capacity. IL-4 receptors were also found on a variety of nonhemopoietic cells such as cloned stromal cell lines from the bone marrow, spleen, thymus, and brain, and on muscle, brain, melanoma, fibroblast, and liver cells. Indeed, only 5 of more than 90 cell types tested have undetectable numbers of IL-4 receptors. The biologic effects of IL-4 on nonhemopoietic cells have not yet been reported and await elucidation.

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