Down-regulation of intestinal lymphocyte activation and Th1 cytokine production by antibiotic therapy in a murine model of Crohn's disease.

Abstract

Resident intestinal bacteria likely play an important role in the pathogenesis of Crohn's disease through their interaction with the gut immune system. SAMP1/YitFc mice spontaneously develop chronic, discontinuous, transmural ileitis with many features similar to Crohn's disease. The aim of this study was to determine the effects and elucidate the mechanisms of action of antibiotic treatment in the SAMP1/YitFc mouse model of ileitis. Mice were treated orally with ciprofloxacin and metronidazole before the development of ileitis (prevention protocol) or after ileitis was fully established (treatment protocol). Terminal ilea were harvested for histological scoring, and lamina propria and mesenteric lymph node cells were isolated for analysis of activation markers and cytokine production. Antibiotic therapy significantly decreased the severity of ileitis both in the prevention (40% reduction, p < 0.05) and the treatment (25% reduction, p < 0.01) protocols, compared with untreated, control mice. These effects were associated with a decreased percentage of CD4(+)/CD45RB(high) lymphocytes in mesenteric lymph nodes of antibiotic-treated mice, as well as decreased production of IFN-gamma (prevention: 0.53 +/- 0.21 vs 1.84 +/- 0.04 ng/ml, p < 0.05; treatment: 8.4 +/- 0.4 vs 12.4 +/- 0.7 ng/ml, p < 0.005) and TNF (prevention: 61.5 +/- 13 vs 134 +/- 19 pg/ml, p < 0.01; treatment: 333.5 +/- 11 vs 496 +/- 20 pg/ml, p < 0.001). The number of activated lamina propria lymphocytes was also reduced after antibiotic treatment. In conclusion, antibiotic therapy significantly ameliorates the severity of ileitis in SAMP1/YitFc mice by a mechanism involving down-regulation of activated gut lymphocytes and inhibition of intestinal Th1 cytokine production.

• Authors: Giorgos Bamias, Marco Marini, Christopher A Moskaluk, Masaru Odashima, William G Ross, Jesús Rivera-Nieves, Fabio Cominelli
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 169 Issue 9 Pg. 5308-14 (Nov 01 2002) ISSN: 0022-1767 [Print] United States
• PMID: 12391251 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Bacterial Agents
• Cytokines
• Metronidazole
• Ciprofloxacin

Topics

• Administration, Oral
• Animals
• Anti-Bacterial Agents
• Cells, Cultured
• Ciprofloxacin (administration & dosage, therapeutic use)
• Crohn Disease (drug therapy, immunology, prevention & control)
• Cytokines (antagonists & inhibitors, biosynthesis)
• Disease Models, Animal
• Down-Regulation (drug effects, immunology)
• Drug Therapy, Combination (administration & dosage, therapeutic use)
• Ileitis (drug therapy, immunology, prevention & control)
• Intestinal Mucosa (drug effects, immunology, metabolism, pathology)
• Lymph Nodes (drug effects, immunology, pathology)
• Lymphocyte Activation (drug effects)
• Mesentery
• Metronidazole (administration & dosage, therapeutic use)
• Mice
• Mice, Inbred Strains
• Th1 Cells (drug effects, immunology, metabolism)