Inhibition of spleen tyrosine kinase as treatment of postoperative ileus

Bree, Sjoerd H. W. van; Gomez‐Pinilla, Pedro J.; Bovenkamp, Fleur S. van de; Giovangiulio, Martina Di; Farro, Giovanna; Némethova, Andrea; Cailotto, Cathy; Jonge, Wouter J. de; Lee, Kevin; Ramírez-Molina, César; Lugo, Dave; Skynner, Michael J.; Boeckxstaens, Guy E.; Matteoli, Gianluca

doi:10.1136/gutjnl-2012-302615

Cited by 29 publications

(19 citation statements)

References 46 publications

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“…The degranulation and consequent release of inflammatory mediators can in turn activate sensory nerves, a phenomenon involved in the pathophysiology of irritable bowel syndrome (IBS) 68 and POI. The use of mast cell stabilizer doxantrazole 69 or an inhibitor of Syk, 70 a kinase involved in the downstream signaling of SP receptors, showed its efficacy in dampening the inflammation in POI in mice. Although the SP-mast cells interaction is a key event in IBS and POI, the neuronal source of this neurotransmitter (i.e., enteric neurons or vagal sensory afferents) remains unclear 71 …”

Section: Intestinal Neuro-immune Interactionsmentioning

confidence: 99%

Neural networks in intestinal immunoregulation

Costes

Boeckxstaens²,

Jonge

et al. 2013

Organogenesis

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Key physiological functions of the intestine are governed by nerves and neurotransmitters. This complex control relies on two neuronal systems: an extrinsic innervation supplied by the two branches of the autonomic nervous system and an intrinsic innervation provided by the enteric nervous system. As a result of constant exposure to commensal and pathogenic microflora, the intestine developed a tightly regulated immune system. In this review, we cover the current knowledge on the interactions between the gut innervation and the intestinal immune system. The relations between extrinsic and intrinsic neuronal inputs are highlighted with regards to the intestinal immune response. Moreover, we discuss the latest findings on mechanisms underlying inflammatory neural reflexes and examine their relevance in the context of the intestinal inflammation. Finally, we discuss some of the recent data on the identification of the gut microbiota as an emerging player influencing the brain function.

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Section: Intestinal Neuro-immune Interactionsmentioning

confidence: 99%

Neural networks in intestinal immunoregulation

Costes

Boeckxstaens²,

Jonge

et al. 2013

Organogenesis

Self Cite

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“…In the mouse small bowel, GSK143 reduced the manipulation-induced production of proinflammatory, macrophage-derived cytokines. Finally, GSK143 improved intestinal transit and reduced recruitment of neutrophils and monocytes to the muscularis externa of the manipulated bowel 9. The inhibitory effects of GSK143 on mast cell and on macrophage are interesting as simultaneous targeting of both cell types might counteract their synergistic actions in POI pathophysiology, enhancing treatment.…”

mentioning

confidence: 99%

“…Mast cell stabilisation with ketotifen or doxantrazole, and macrophage inhibition with semapimod improved the inflammatory-dysmotility component of POI in a clinical trial7 and an animal study 8. Van Bree et al 9 investigated the therapeutic effect of a novel spleen tyrosine kinase inhibitor GSK143 on cultured mast cells and macrophages and in mouse POI. Their in vitro results demonstrate that GSK143 can inhibit mediator release from mast cells evoked either by Substance P or by IgE crosslinking, indicating broad inhibition of mediator release.…”

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confidence: 99%

Intestinal inflammation in postoperative ileus: pathogenesis and therapeutic targets

Rychter

Clavé

2013

Gut

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“…The mechanism of POI is complex, characterized mainly by intestinal inflammatory infiltration343536. In traditional Chinese medicine, SMD and acupuncture at the tsusanli acupoint have long been used to reduce risk of POI and manage various functional gastrointestinal disorders8937.…”

Section: Discussionmentioning

confidence: 99%

Comparison of efficacy of simo decoction and acupuncture or chewing gum alone on postoperative ileus in colorectal cancer resection: a randomized trial

Yang

Zuo

Zhao

et al. 2017

Sci Rep

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To compared the ability of chewing gum or simo decoction (SMD) and acupuncture to reduce incidence of postoperative ileus (POI) after colorectal cancer resection, patients with colorectal cancer undergoing open or laparoscopic resection were randomized to receive SMD and acupuncture (n = 196), chewing gum alone (n = 197) or no intervention (n = 197) starting on postoperative day 1 and continuing for 5 consecutive days. Patients treated with SMD and acupuncture experienced significantly shorter hospital stay, shorter time to first flatus and shorter time to defecation than patients in the other groups (all P < 0.05). Incidence of grade I and II complications was also significantly lower in patients treated with SMD and acupuncture. Patients who chewed gum were similar to those who received no intervention in terms of hospital stay, incidence of complications, and time to first bowel motion, flatus, and defecation (all P > 0.05). The combination of SMD and acupuncture may reduce the incidence of POI and shorten hospital stay for patients with colorectal cancer after resection. In contrast, chewing gum does not appear to affect recovery of bowel function or hospital stay, though it may benefit patients who undergo open resection. (Clinicaltrials.gov registration number: NCT02813278).

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Inhibition of spleen tyrosine kinase as treatment of postoperative ileus

Abstract: The Syk inhibitor GSK143 reduces macrophage activation and mast cell degranulation in vitro. In addition, it inhibits manipulation-induced intestinal muscular inflammation and restores intestinal transit in mice. These findings suggest that Syk inhibition may be a new tool to shorten POI.

Cited by 29 publications

References 46 publications

Neural networks in intestinal immunoregulation

Neural networks in intestinal immunoregulation

Intestinal inflammation in postoperative ileus: pathogenesis and therapeutic targets

Comparison of efficacy of simo decoction and acupuncture or chewing gum alone on postoperative ileus in colorectal cancer resection: a randomized trial

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