• Philip Plaeke, Joris G De Man, Annemieke Smet, Surbhi Malhotra-Kumar, Isabel Pintelon, Jean-Pierre Timmermans, Sara Nullens, Philippe G Jorens, Guy Hubens, and Benedicte Y De Winter.
• Laboratory of Experimental Medicine and Pediatrics (LEMP), University of Antwerp, Antwerp, Belgium.
• Neurogastroenterol. Motil. 2020 Mar 1; 32 (3): e13754.

BackgroundSepsis is a severe pathological condition associated with systemic inflammation, intestinal inflammation, and gastrointestinal barrier dysfunction. Intestinal alkaline phosphatase (IAP) has been demonstrated to detoxify lipopolysaccharide, an important mediator in the pathophysiology of sepsis. We investigated the effect of treatment with IAP on intestinal permeability, intestinal inflammation, and bacterial translocation.MethodsOF-1 mice were divided into 4 groups (n = 12/group), undergoing either a sham or cecal ligation and puncture (CLP) procedure to induce sepsis. Mice received IAP or a vehicle intraperitoneally 5 minutes prior to the onset of the CLP or sham procedure, which was repeated every 12 hours for two consecutive days. After two days, in vivo intestinal permeability, intestinal inflammation, and bacterial translocation were determined.Key ResultsCLP-induced sepsis resulted in significantly more weight loss, worse clinical disease scores, bacterial translocation, and elevated inflammatory cytokines. Intestinal permeability was increased up to 5-fold (P < .001). IAP activity was significantly increased in septic animals. Treatment with IAP had no effect on clinical outcomes but reduced the increased permeability of the small intestine by 50% (P = .005). This reduction in permeability was accompanied by a modified gene expression of claudin-1 (P = .025), claudin-14 (P = .035), and interleukin 12 (P = .015). A discriminant analysis showed that treatment with IAP is linked to modified mRNA levels of several tight junction proteins and cytokines.Conclusions And InferencesTreatment with IAP diminished CLP-induced intestinal barrier disruption, associated with modified expression of several cytokines and claudins. Nevertheless, this effect did not translate into better clinical outcomes in our experimental setup.© 2019 John Wiley & Sons Ltd.

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