Clostridium difficile infection aggravates colitis in interleukin 10-deficient mice.

Abstract:

AIM:To investigate the effect of Clostridium difficile (C. difficile) infection in an interleukin 10-deficient (IL-10(-/-)) mouse model of inflammatory bowel disease. METHODS:Bone marrow-derived dendritic cells isolated from wild type (WT) and IL-10(-/-)mice were stimulated for 4 h with C. difficile toxin A (200 μg/mL), and gene expression of interferon (IFN)-γ, IL-12 and IL-23 was determined by real-time reverse transcription polymerase chain reaction. WT and IL-10(-/-) mice (n = 20 each) were exposed to an antibiotic cocktail for three days and then were injected with clindamycin (i.p.). Mice (n = 10 WT, 10 IL-10(-/-)) were then challenged with oral administration of C. difficile (1 × 10(5) colony forming units of strain VPI 10463). Animals were monitored daily for 7 d for signs of colitis. Colonic tissue samples were evaluated for cytokine gene expression and histopathologic analysis. RESULTS:C. difficile toxin A treatment induced IFN-γ gene expression to a level that was significantly higher in BDMCs from IL-10(-/-) compared to those from WT mice (P < 0.05). However, expression of IL-12 and IL-23 was not different among the groups. Following C. difficile administration, mice developed diarrhea and lost weight within 2-3 d. Weight loss was significantly greater in IL-10(-/-) compared to WT mice (P < 0.05). C. difficile infection induced histopathologic features typical of colitis in both IL-10(-/-) and WT mice. The histopathologic severity score was significantly higher in the IL-10(-/-) than in WT mice (mean ± standard error; 5.50 ± 0.53 vs 2.44 ± 0.46; P < 0.05). This was accompanied by a significantly greater increase in IFN-γ gene expression in colonic tissues from IL-10(-/-) than from WT mice challenged with C. difficile (P < 0.05). CONCLUSION:These results indicate that colitis is more severe after C. difficile infection in IL-10(-/-)mice, and that IFN-γ expression is involved in this process.

journal_name

World J Gastroenterol

authors

Kim MN,Koh SJ,Kim JM,Im JP,Jung HC,Kim JS

doi

10.3748/wjg.v20.i45.17084

subject

Has Abstract

pub_date

2014-12-07 00:00:00

pages

17084-91

issue

45

eissn

1007-9327

issn

2219-2840

journal_volume

20

pub_type

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