Treatment with Met-RANTES decreases bacterial translocation in experimental colitis

doi:10.1016/j.amjsurg.2005.10.005

The American Journal of Surgery

Volume 191, Issue 1, January 2006, Pages 77-83

https://doi.org/10.1016/j.amjsurg.2005.10.005 Get rights and content

Abstract

Background

During colitis, epithelial function is impaired, leading to increased bacterial translocation. Recent studies have shown the important role of proinflammatory cytokines and chemokines, including RANTES (regulated on activation, normal T-cell expressed and secreted), in inflammatory bowel diseases (IBDs). In this study, we evaluated the role of Met-RANTES, an antagonist of the RANTES receptor, on the impairment of bacterial translocation in a rat model of colitis.

Methods

Rats were randomly assigned to 3 groups. group 1 = control, group 2 = experimental colitis, and group 3 = colitis plus Met-RANTES treatment. On day 7 after colitis was induced, plasma tumor necrosis factor-α colon tissue myeloperoxidase and portal blood endotoxin levels were measured. Lymph node, liver, and spleen culture quantified bacterial translocation.

Results

Met-RANTES treatment resulted in significant decreases in colonic damage as well as bacterial translocation in experimental colitis.

Conclusions

These results suggest that chemokine receptor antagonists may potentially be useful in the treatment of IBDs.

Section snippets

Animal preparation

The study was performed at Erciyes University Hakan Cetinsaya Experimental Research Centre. Forty-five male Wistar albino rats bred in the same research center, weighing between 180 and 210 g at 25 to 30 weeks of age, were used for this study. The rats were fed a standard chow pellet diet, had free access to water, and were maintained on a 12-hour light-to-dark cycle. Water only was provided during the 12 hours preceding the experiments. The Animal Care Committee of the University of Erciyes

Results

Plasma TNF-α and endotoxin levels in the colitis and Met-RANTES groups were significantly increased at day 8 compared with the control groups (P < .01). The increase in the Met-RANTES group was significantly less than the increase in the colitis group (P < .01; Fig. 1).

In the control group, no bacterial growth was detected at day 8. TNBS-E colitis caused a significant increase in the frequencies of bacterial translocation in liver, spleen, MLNs, and portal blood. Compared with the colitis

Comments

CD and UC are the 2 major clinical forms of IBD in developed countries, affecting mostly young people in a chronic and often debilitating way. Symptoms include diarrhea, weight loss, and abdominal pain. An increase in incidence has been noticed in the last decade, and the actual combined prevalence of IBDs is now estimated to be 150 to 200/100,000 people in Europe and North America [23].

Although experimental animal models of colitis are of value in eliciting some of the mechanisms of IBDs, the

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Rats in the control group formed extensive adhesions. In comparison with the control group, the adhesion scores were significantly lower in the 2 other groups. The immunohistochemical grading scores of vascular endothelial growth factor correlated closely with the total adhesion scores and were less in groups 2 and 3 (P < .005).
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Furthermore, the CCR5 receptor seems to be responsible for fever in response to RANTES, since a specific antibody against this receptor blocked fever induced by the chemokine (Tavares and Miñano, 2004). The addition of a single methionine on the amino terminal of RANTES resulted in the production of Met-RANTES, a potent antagonist of CCR1 and CCR5 receptors (Proudfoot et al., 1999a), which is effective in reducing inflammation in rodent models of renal inflammation (Grone et al., 1999), reducing collagen-induced arthritis (Plater-Zyberk et al., 1997) and reducing significantly the colonic damage and bacterial translocation in experimental colitis (Kucuk et al., 2006). In view of these considerations, the present study investigated the involvement of CCR1 and CCR5 chemokine receptors in the febrile response induced by LPS by treating rats with Met-RANTES.
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Scientific papers–clinical (international)Treatment with Met-RANTES decreases bacterial translocation in experimental colitis

Abstract

Background

Methods

Results

Conclusions

Section snippets

Animal preparation

Results

Comments

Lancet

J Biol Chem

Gastroenterology

Kidney Int

Gastroenterology

J Invest Dermatol

Lancet

Am J Gastroenterol

Lancet

Recent developments in the immunology of inflammatory bowel disease

Scand J Immunol

Significance of systemic endotoxaemia in inflammatory bowel disease

Gut

Endotoxaemia in active Crohn’s disease. Treatment with whole gut irrigation and 5-aminosalicylic acid

Gut

Incidence of pathogenic bacteria from mesenteric lymph nodes and ileal serosa during Crohn’s disease surgery

Br J Surg

Serum antibodies to Escherichia coli in subjects with ulcerative colitis

Clin Exp Immunol

Experimental models of inflammatory bowel disease

Gastroenterology

The chemokine RANTES is a crucial mediator of the progression from acute to chronic colitis in the rat

J Immunol

Differential in situ expression of the genes encoding the chemokines MCP-1 and RANTES in human inflammatory bowel disease

J Pathol

Chemokines and leukocyte traffic

Nature

Scientific papers–clinical (international)
Treatment with Met-RANTES decreases bacterial translocation in experimental colitis