The role of leucocytes in the induction of fluid secretion by Salmonella typhimurium

Departments of Microbiology, University of Birmingham, PO Box 363, Birmingham B15 2TT * Departments of Microbiology Immunology, University of Birmingham, PO Box 363, Birmingham B15 2TT Departments of Microbiology Physiology, University of Birmingham, PO Box 363, Birmingham B15 2TT Institute of Child Health, Francis Road, Birmingham B16 8ET 1 Correspondence should be sent to: Dr J. Stephen, Department of Microbiology, University of Birmingham, PO Box 363, Birmingham B15 2TT. Received February 2, 1989 Accepted July 12, 1989 Nitrogen mustard (N 2 M) treatment of rabbits induced neutropenia, and, in ligated ileal loops, it inhibited fluid secretion induced by salmonella or by cholera toxin (CT). Pretreatment of rabbits with indomethacin almost abolished salmonella-induced fluid secretion and significantly reduced that induced by CT. Similar effects of N 2 M and indomethacin on fluid secretion induced by salmonella, but not by CT, have been reported by other workers and used to implicate prostaglandins, from the salmonella-induced inflammation, as mediators of fluid secretion. In contrast, we show that N 2 M treatment, in addition to reducing CT-induced secretion, caused severe morphological alterations to ileal mucosa. Irradiation techniques were developed for inducing neutropenia, but they did not totally inhibit salmonella-induced leucocyte influx into ileal mucosa. We propose an alternative mechanism for the inhibitory effect of N 2 M on salmonella- and CT-induced secretion, based on the known anti-mitotic activity of N 2 M. Also, the anti-secretory effect of indomethacin cannot be attributed uniquely to its anti-inflammatory activity because it depressed CT-induced secretion as well as salmonella-induced secretion. These results support the concept of pathophysiological secretion in infectious diarrhoea, developed previously for rotavirus and extended to bacterial infections. Present address: Institute of Epidemiology and Microbiology, PO Box 5, Changping, Beijing, China.