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(200μg/m L),and gene expression of interferon(IFN)-γ,IL-12 and IL-23was determined by real-time reverse transcription polymerase chain reaction.WT and IL-10-/-mice(n=20each)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(1×105 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-γgene 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-γgene 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-γexpression is involved in this process. 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 ) 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 ec) were exposed to an antibiotic cocktail for three days and then were injected with clindamycin (ip) - / -) 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 days 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 t Of those from WT mice (P <0.05) .Wowever, expression of IL-12 and IL-23 was not different among the groups. Foliar 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 histopathological features typical of colitis in both IL-10 - / - and WT mice.The histopathological 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- / -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-γexpression is involved in this process.