Rie Hanaoka

The water-soluble extract from cultured medium of Ganoderma lucidum (Reishi) mycelia (Designated as MAK) ameliorates murine colitis induced by trinitrobenzene sulphonic acid.

Ganoderma lucidum Karst is well known as ‘Reishi’, a traditional food in China and Japan. It contains a polysaccharide component known to induce granulocyte macrophage colony‐stimulating factor (GM‐CSF) production from murine splenocytes. Moreover, GM‐CSF may be a therapeutic agent for Crohn’s disease. In this study, we investigated the water‐soluble, polysaccharide components of Reishi (designated as MAK) in murine colitis induced by trinitrobenzene sulphonic acid (TNBS). We examined the concentration of GM‐CSF in peritoneal macrophage cells (PMs) of C57BL/6 mice during in vitro and in vivo stimulation with MAK. After feeding with chow or MAK for 2 weeks, 2 mg of TNBS/50% ethanol was administered to each mouse. After 3 days of TNBS treatment, intestinal inflammation was evaluated, and mononuclear cells of the mesenteric lymph nodes (MLNs) and colon were cultured for ELISA. To determine the preventive role of GM‐CSF, the mice were pre‐treated with or without anti‐GM‐CSF antibody before TNBS administration. In vitro and in vivo MAK‐stimulated PMs produced GM‐CSF in a dose‐dependent manner. Intestinal inflammation by TNBS was improved by feeding with MAK. MLNs of mice treated with TNBS produced IFN‐γ, which was inhibited by feeding with MAK. In contrast, MLNs of mice treated with TNBS inhibited GM‐CSF production, which was induced by feeding with MAK. The colon organ culture assay also revealed that IFN‐γ was decreased and GM‐CSF was increased by MAK. The preventive effect was blocked by the neutralization of GM‐CSF. We concluded that the induction of GM‐CSF by MAK may provide the anti‐inflammatory effect.

Role of Natural Killer T Cells in the Mouse Colitis‐Associated Colon Cancer Model

Invariant natural killer T (iNKT) cells are considered innate‐like lymphocytes, and regulate the immunity against inflammation and tumorigenesis. However, the impact of iNKT cells in inflammation‐associated tumorigenesis remains unclear. In this study, we examined the physiological role of iNKT cells in a mouse colitis‐associated colorectal cancer model. C57BL/6 (B6) and Jα18 NKT cell‐deficient KO (KO) mice were used. Colitis‐associated colorectal cancer was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). The resulting inflammation and tumours were examined. The surface markers of mononuclear cells from the liver and the colon were assessed by FACS. The levels of IL‐13 from the colon were measured by ELISA. α‐galactosylceramide (GC), or its close analog OCH, was administered intraperitoneally on the first day of each cycle of DSS‐administration. In the AOM/DSS model, hepatic iNKT cells were significantly decreased. In KO mice there were significantly greater numbers of colon tumours and more severe inflammation than in B6 mice. FACS analysis revealed that the population of NK1.1 + T cells (non‐invariant NKT cells) in the colon was increased when compared to B6 mice. The secretion of IL‐13 was increased in the colon of KO mice after AOM/DSS. The number of colon tumours was significantly decreased in the GC‐treated group compared to the control group. GC‐treatment significantly inhibited IL‐13 secretion from the colonic mononuclear cells and the number of colonic NK1.1 + T cells was significantly decreased. These results suggest that iNKT cells may play a critical role in the prevention of tumour progression and inflammation in the AOM/DSS model.

Intestinal Tuberculosis with Hoarseness as a Chief Complaint due to Mediastinal Lymphadenitis

A 68-year-old woman was admitted to our hospital complaining of hoarseness. A chest X-ray detected an abnormal shadow on the upper right lung. Bronchoscopic examination revealed that the left vocal cord was fixed in the paramedian position, and therefore left recurrent nerve paralysis was suspected. Lymphadenopathy was found in the left supraclavicular area. Chest computed tomography showed that the pretracheal and subaortic lymph nodes were swollen. Gastroendoscopy showed a 2-cm protruding lesion with ulceration on the upper esophagus. Histological examination of the supraclavicular lymph nodes and biopsy specimens from the esophagus revealed non-specific inflammation. PET-CT showed abnormal accumulations not only on the upper right lung but also on the lower right of the abdomen. Colonoscopy was performed and multiple erosions on the terminal ileum were found. Polymerase chain reaction analysis of a specimen biopsied from the erosion of the terminal ileum was positive for Mycobacterium tuberculosis and intestinal tuberculosis was diagnosed. The patient was then treated with anti-tuberculous therapy. After treatment, the erosions on the terminal ileum, the swelling of the mediastinal lymphadenopathy, and the esophageal ulcer were all improved. The hoarseness was subsequently relieved. This is the first report of intestinal tuberculosis with hoarseness as a chief complaint due to mediastinal lymphadenitis.

Cheilitis granulomatosa as an early manifestation of Crohn's disease.

Cheilitis granulomatosa (CG) is a rare disease, which presents usually as a persistent swelling of the soft tissues in the orofacial region and is characterized histologically by a granulomatous inflammation. We report the case of a 19-year-old man who suffered from anal fistula. The patient had a 6-year history of asymptomatic and persistent swelling of the lower lip. Examinations for gastrointestinal lesions containing double-balloon total enteroscopy revealed erosions located longitudinally throughout the small intestine and the patient was diagnosed Crohn’s disease (CD). Biopsy of the lower lip showed non-caseating granuloma and confirmed the diagnosis of CG. Despite an elemental diet and mesalazine therapy, the lip swelling persisted. The CG can be the first presenting symptom of CD. CG as a complication of CD is discussed.