BACKGROUND/AIMS: Recent research has highlighted the importance of interactions between commensal fungi and intestinal inflammation. However, there are few studies investigating whether commensal fungi contribute to inflammation in patients with Crohn's disease (CD). The aim of this study is to investigate reveal interactions between commensal fungi and host immune cells in CD. METHODS: CD14-positive monocytes were isolated from peripheral blood mononuclear cells from healthy human volunteers and then differentiated in the presence of macrophage colony-stimulating factor (M-CSF) (referred to as M-macrophages, M-Mϕs) or M-CSF and interferon-γ (IFN-γ) (referred to as M-gamma macrophages, Mγ-Mϕs). Cytokine production by these in vitro differentiated macrophages in response to β-(1,3)-glucan was analyzed by flow cytometry. Expression of Dectin-1 was examined using flow cytometry, western blotting, and quantitative reverse transcription-polymerase chain reaction. Cytokine production by in vitro differentiated macrophages in response to β-(1,3)-glucan was measured in the presence of an anti-Dectin-1 receptor antagonist, anti-Syr, or an anti-Fas-1 antibody. Cytokine production by lamina propria mononuclear cells (LPMCs) derived from CD patients in response to β-(1,3)-glucan was also analyzed. RESULTS: Mγ-Mϕs produced a large amount of tumor necrosis factor-α (TNF-α) and interleukin-6 in response to β-(1,3)-glucan. Dectin-1 expression was significantly higher in Mγ-Mϕs than in M-Mϕs. The increase in TNF-α production by Mγ-Mϕs stimulated with glucan was reversed by blocking Dectin-1, Syr or Fas-1. LPMCs derived from CD patients stimulated with β-(1,3)-glucan produced significantly higher amount of TNF-α than LPMCs derived from UC patients. CONCLUSIONS: These results suggest that commensal fungal microbiota may contribute to the pathogenesis of CD by inducing macrophages-derived pro-inflammatory cytokines.
Blotting, Western ; Candida albicans* ; Candida* ; Crohn Disease* ; Cytokines* ; Flow Cytometry ; Fungi ; Healthy Volunteers ; Humans ; In Vitro Techniques ; Inflammation ; Interleukin-6 ; Macrophage Colony-Stimulating Factor ; Macrophages* ; Microbiota ; Monocytes ; Mucous Membrane* ; Necrosis ; Tumor Necrosis Factor-alpha

We report a case of a 57-year-old woman with radiation proctitis (RP) treated by shiunko (SK) enema with promising outcomes. The patient underwent interstitial brachytherapy for anterior vaginal vault recurrence of uterine cancer. Nine months after the treatment, she had anal pain and was diagnosed with RP by clinical course and colonoscopy. The rectal ulcer was so severe that a surgeon proposed permanent stoma formation as one option, given eventual risk of rectovaginal fistula. The patient rejected stoma formation and opted for Kampo medicine. Though she took keishibukuryogankayokuinin for blood stasis at first, her anal pain and rectal bleeding gradually worsened. Thereafter, she mainly used SK enema, kyukikyogaito and magnesium oxide. Anal pain and rectal bleeding decreased after applying SK to the rectal wall per rectum. Magnetic resonance imaging (MRI) and colonoscopy findings of the rectal ulcer also improved. SK effectively reduced anal pain and rectal bleeding as well as stimulated tissue repair in our patient, and therefore SK is worth considering in the treatment of RP.