Indomethacin Inhibition of Salmonella typhimurium, Shigella flexneri, and Cholera-Mediated Rabbit Ileal Secretion

Gots, Ronald E.; Formal, Samuel B.; Giannella, Ralph A.

doi:10.1093/infdis/130.3.280

Cited by 117 publications

(46 citation statements)

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“…The indomethacin data substantiate the findings of Gots et al (1974) with S.typhimurium and CT. However, the present data and those of Wallis et al (1989) suggest that if prostaglandins are involved in either S.typhimurium-or CT-induced fluid secretion, they are unlikely to be of neutrophil origin.…”

Section: Discussionsupporting

confidence: 81%

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

Wallis

Vaughan

Clarke

et al. 1990

Journal of Medical Microbiology

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Summary. Nitrogen mustard (N2M) 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 salmonellainduced fluid secretion and significantly reduced that induced by CT. Similar effects of N2M 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 N2M 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 salmonellainduced leucocyte influx into ileal mucosa. We propose an alternative mechanism for the inhibitory effect of N2M on salmonella-and CT-induced secretion, based on the known anti-mitotic activity of N2M. 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.

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Section: Discussionsupporting

confidence: 81%

“…The method used was that described by Gots et al (1974) with minor modification. Indomethacin 0.5 g was dissolved in 10 ml of ethanol 100% by sonication (Hilsonic water bath, Chromatography Services Ltd, Wirral) for 30 min, and added to 90 ml of 0 .…”

Section: Use Of Indomethacin To Modify Fluid Secretionmentioning

confidence: 99%

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

Wallis

Vaughan

Clarke

et al. 1990

Journal of Medical Microbiology

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“…Gots et al (1974) showed that if rabbits were pre-treated with indomethacin, fluid secretion in ileal loops challenged with S . typhirnuriurn was almost completely inhibited, whereas bacterial invasion and the accompanying inflammatory cell influx appeared normal.…”

Section: Introductionmentioning

confidence: 99%

Quantification of the leucocyte influx into rabbit ileal loops induced by strains of Salmonella typhimurium of different virulence

Wallis

Hawker

Candy

et al. 1989

Journal of Medical Microbiology

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“…However, because mice are resistant to intestinal infection with Shigella, the model is not fully appropriate to address the anti-inflammatory properties of SIgA in mucosal tissues. Hence, in the current study, we used the rabbit model of ligated ileal loops infected with Shigella because it mimics both local inflammation and subsequent massive tissue destruction as it occurs during natural infection in humans (24,27). Although this model has intrinsic limitations due to the restricted number of available immunologic reagents, it turned out to be very helpful to demonstrate that specific SIgA is a key player to reduce the proinflammatory response turned on by Shigella at the level of the intestinal barrier in vivo.…”

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confidence: 99%

Secretory IgA-Mediated Neutralization of Shigella flexneri Prevents Intestinal Tissue Destruction by Down-Regulating Inflammatory Circuits

Boullier

Tanguy

Kadaoui

et al. 2009

The Journal of Immunology

157

132

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Shigella, a Gram-negative invasive enteropathogenic bacterium responsible for bacillary dysentery, causes the rupture, invasion, and inflammatory destruction of the human colonic mucosa. We explored the mechanisms of protection mediated by Shigella LPS-specific secretory IgA (SIgA), the major mucosal Ab induced upon natural infection. Bacteria, SIgA, or SIgA-S. flexneri immune complexes were administered into rabbit ligated intestinal loops containing a Peyer’s patch. After 8 h, localizations of bacteria, SIgA, and SIgA-S. flexneri immune complexes were examined by immunohistochemistry and confocal microscopy imaging. We found that anti-Shigella LPS SIgA, mainly via immune exclusion, prevented Shigella-induced inflammation responsible for the destruction of the intestinal barrier. Besides this luminal trapping, a small proportion of SIgA-S. flexneri immune complexes were shown to enter the rabbit Peyer’s patch and were internalized by dendritic cells of the subepithelial dome region. Local inflammatory status was analyzed by quantitative RT-PCR using newly designed primers for rabbit pro- and anti-inflammatory mediator genes. In Peyer’s patches exposed to immune complexes, limited up-regulation of the expression of proinflammatory genes, including TNF-α, IL-6, Cox-2, and IFN-γ, was observed, consistent with preserved morphology. In contrast, in Peyer’s patches exposed to Shigella alone, high expression of the same mediators was measured, indicating that neutralizing SIgA dampens the proinflammatory properties of Shigella. These results show that in the form of immune complexes, SIgA guarantees both immune exclusion and neutralization of translocated bacteria, thus preserving the intestinal barrier integrity by preventing bacterial-induced inflammation. These findings add to the multiple facets of the noninflammatory properties of SIgA.

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Indomethacin Inhibition of Salmonella typhimurium, Shigella flexneri, and Cholera-Mediated Rabbit Ileal Secretion

Cited by 117 publications

References 0 publications

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

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

Quantification of the leucocyte influx into rabbit ileal loops induced by strains of Salmonella typhimurium of different virulence

Secretory IgA-Mediated Neutralization of Shigella flexneri Prevents Intestinal Tissue Destruction by Down-Regulating Inflammatory Circuits

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