Ulcerative Colitis: Hibi T

Naganuma M, Hibi T. · No affiliation provided · J Gastroenterol. · Pubmed #11993519 No free full text.

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Matsumoto T, Iwao Y, Igarashi M, Watanabe K, Otsuka K, Watanabe T, Iizuka B, Hida N, Sada M, Chiba T, Kudo SE, Oshitani N, Nagawa H, Ajioka Y, Hibi T. · Department of Lower Gastroenterology, Hyogo College of Medicine, Nishinomiya, Japan. · Inflamm Bowel Dis. · Pubmed #17973300 links to  free full text

Abstract: Clinical and epidemiological studies have revealed that the incidence of colorectal cancer associated with ulcerative colitis increases with long-term chronic inflammation. Careful endoscopic observation and histological studies to check for dysplasia in the colon are important in detecting neoplasia. Current surveillance protocols mainly involve frequent step biopsies to yield a reasonable rate of dysplasia detection. However, recent studies using chromoendoscopy or magnifying endoscopy have proposed that neoplastic changes may be detected efficiently. Therefore, it is very important to understand the typical endoscopic findings found in neoplastic changes in patients proven to have long-standing ulcerative colitis. In this review, we demonstrate the typical endoscopic findings by conventional endoscopy and chromoendoscopy.

Ogata H, Hibi T. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #17675817 No free full text.

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Kanai T, Hibi T, Watanabe M. · Department of Gastroenterology and Hepatology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan. · Expert Opin Biol Ther. · Pubmed #16610976 No free full text.

Abstract: Ulcerative colitis (UC) and Crohn's disease (CD) are debilitating idiopathic inflammatory bowel diseases (IBDs) with symptoms that impair ability to function and quality of life. The aetiology of IBD is inadequately understood and, therefore, drug therapy has been empirical instead of based on sound understanding of the disease mechanisms. This has been a major factor for poor drug efficacy and treatment-related side effects that often add to disease complications. The development of biologicals, notably infliximab, to block TNF-alpha reflects some progress, but there is major concern about their side effects and lack of long-term safety and efficacy profiles. However, IBD by its very nature is exacerbated and perpetuated by inflammatory cytokines, including TNF-alpha, IL-6 and IL-12, for which activated peripheral blood lymphocytes, monocytes/macrophages and granulocytes are major sources. Hence, activated leukocytes should be appropriate targets of therapy. At present, three strategies are available for removing excess and activated leukocytes by leukocytapheresis: centrifugation, Adacolumn and Cellsorba. Centrifugation can deplete lymphocytes or total leukocytes, whereas Adacolumn selectively adsorbs granulocytes and monocytes together with a smaller fraction of lymphocytes (FcgammaR- and complement receptor-bearing leukocytes), and Cellsorba non-selectively removes all three major leukocyte populations. Efficacy has ranged from 'none' to an impressive 93% together with excellent safety profiles and downmodulation of inflammation factors. Furthermore, leukocytapheresis has shown strong drug-sparing effects and reduced the number of patients requiring colectomy or exposure to unsafe immunosuppressants, such as cyclosporin A. Leukocytapheresis removes from the body cells that contribute to IBD and, therefore, unlike drugs, it is not expected to induce dependency or refractoriness.

Matsuoka K, Hibi T. · Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Keio University. · Nippon Rinsho. · Pubmed #15954400 No free full text.

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Hisamatsu T, Hibi T. · Department of Internal Medicine, Keio University School of Medicine. · Nippon Rinsho. · Pubmed #15881178 No free full text.

Abstract: Ulcerative colitis (UC) has been known as inflammatory bowel disease. Progress in UC management strategies has led to optimized approaches for achieving the two primary clinical goals of therapy: induction and maintenance of remission. We here review about immunosuppressants in management of UC; Cyclosporine A (CsA) has been used for the induction therapy in steroid resistant refractory UC. Although it has been reported that CsA has high response rate in severe UC, long-term efficacy (maintenance of remission) has not been proven. To improve maintenance therapy, immunosuppressant has been re-considered in management of UC. In recent years, it has been reported that efficacy of 6-mercaptopurine/azathioprine in maintenance of remission of UC is superior to 5-aminosalicylate (5-ASA). Pharmacological studies have indicated thiopurine methyltransferase (TPMT) activity is essential for maintenance of blood concentration of 6-thioguanine nucleotide (6-TG).

Hibi T, Ogata H. · No affiliation provided · Nippon Naika Gakkai Zasshi. · Pubmed #15052810 No free full text.

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Hibi T, Inoue N, Ogata H, Naganuma M. · Department of Internal Medicine, Keio University School of Medicine, Center for the Research of Inflammatory Bowel Disease, Keio University School of Medicine, Tokyo, Japan. · J Gastroenterol. · Pubmed #12698869 No free full text.

Abstract: Ulcerative colitis (UC) and Crohn's disease (CD) comprise a series of inflammatory bowel disease (IBD) resulting from chronic upregulation of the mucosal immune system. Although the pathogenesis of IBD remains elusive, it appears that there is chronic activation of the immune and inflammatory cascade in genetically susceptible individuals. Current disease management guidelines have therefore focused on the use of antiinflammatory agents, aminosalicylates and corticosteroids. However, some patients are still refractory to these therapies. Recent advances in the understanding of the pathophysiological conditions of IBD have provided new immune system modulators as therapeutic tools. Cytapheresis has demonstrated effectiveness against UC and has practical use in Japan. Immunosuppressive agents including cyclosporin A and tacrolimus (FK506) have expanded the choice of medical therapies available for certain subgroups of patients. Furthermore, biological therapies have begun to assume a prominent role. Studies with chimeric monoclonal anti-TNF-alpha antibody treatment of CD have been reported with dramatic success. Another antiinflammatory cytokine therapy includes anti-IL-6 receptor, anti-IL-12, or toxin-conjugated anti-IL-7 receptor. Given the diversity of proinflammatory products under its control, NF-kappa B may be viewed as a master switch in lymphocytes and macrophages, regulating inflammation and immunity. In the murine 2,4,6-trinitrobenzen sulfonic acid (TNBS) colitis model, an antisense oligonucleotide to NF-kappa B p65 ameliorated inflammation even after induction of colitis. Recently, a clinical pilot trial of this agent demonstrated promising results. Accumulating evidence suggests that luminal bacterial flora is a requisite and central factor in the development of IBD. Probiotic therapies such as a nonpathogenic Escherichia coli strain have been well tolerated, but larger clinical trials are needed. In addition, novel therapeutic strategies targeting adhesion molecules and costimulatory molecules, or enhancing tissue repair, are under investigation. Although some still need more confirmatory studies, these immune therapies will provide new insights into cell-based and gene-based treatment against IBD in the near future.

Hibi T, Inoue N, Ogata H. · No affiliation provided · Nippon Naika Gakkai Zasshi. · Pubmed #12577929 No free full text.

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Hibi T, Inoue N. · Departmetn of Internal Medicine, School of Medicine, Keio University. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #11400268 No free full text.

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Hibi T, Naganuma M. · No affiliation provided · Nippon Naika Gakkai Zasshi. · Pubmed #11307526 No free full text.

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Hibi T, Takagi H. · Department of Internal Medicine, Keio University School of Medicine, Center for Research of Inflammatory Bowel Disease. · Ryoikibetsu Shokogun Shirizu. · Pubmed #11269059 No free full text.

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Watanabe M, Ueno Y, Yamazaki M, Hibi T. · Keio Cancer Center, Tokyo, Japan. · Immunol Res. · Pubmed #10741865 No free full text.

Abstract: We have demonstrated that intestinal epithelial cells produce interleukin-7 (IL-7) and IL-7 serves as a regulatory factor for proliferation of mucosal lymphocytes. To clarify the mechanism by which locally produced IL-7 regulates mucosal lymphocytes and the role of mucosal IL-7 in colonic inflammation, we investigated IL-7 transgenic (IL-7 Tg) mice and demonstrated that IL-7 Tg mice developed acute and chronic colitis with histopathological similarity to ulcerative colitis in humans. In concert with our recent findings that IL-7 stimulates the proliferation of inactivated mucosal lymphocytes but eliminates activated lymphocytes in the inflamed mucosa of human ulcerative colitis. These findings suggest that chronic inflammation in the colonic mucosa is mediated by dysregulation of epithelial cell-derived IL-7 system.

Iwakami Y, Sakuraba A, Sato T, Takada Y, Izumiya M, Ichikawa H, Hibi T. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. · Ther Apher Dial. · Pubmed #19379153 No free full text.

Abstract: The aim of this study was to elucidate the molecular mechanisms responsible for the therapeutic effects of granulocyte and monocyte adsorption apheresis (GMA). We investigated the alterations in circulating monocyte subsets and monocyte-derived dendritic cell (moDC) function after GMA therapy in ulcerative colitis (UC) patients. Eighteen patients with UC were enrolled: 14 patients were responders, and 4 patients were non-responders. Peripheral venous blood was obtained within 5 min before and 5 min after GMA therapy. Flow cytometric analysis for monocyte markers (CD14/CD16) was then performed. Monocyte-derived dendritic cells were obtained and alterations in their phenotype were analyzed by flow cytometry. Their function was also analyzed in a mixed lymphocyte reaction assay between allo-naïve T lymphocytes. Flow cytometric analysis for intracellular interferon (IFN)-gamma (T-helper 1 cells) and interleukin (IL)-4 (T-helper 2 cells) was then performed for the stimulated T lymphocytes. In patients who responded to GMA, the average numbers of monocytes, especially CD16(+) monocytes, were significantly decreased after therapy (P < 0.05). In responders, post-GMA moDCs expressed significantly lower CD80 and B7-DC, which are one of the stimulation and maturation markers of dendritic cells, compared to pre-GMA moDCs. CD83, CD86 and human leukocyte antigen-DR also showed a tendency to decrease. In responders, naïve T lymphocytes stimulated with post-GMA moDCs produced significantly less IFN-gamma and IL-4 compared to those stimulated with pre-GMA moDCs. The results of our study show that some of the immunosuppressive effects of GMA therapy may be associated with the modulation of monocyte subsets and moDC function.

Sawada K, Kusugami K, Suzuki Y, Bamba T, Munakata A, Hibi T, Shimoyama T. · Department of Gastroenterology, Hyogo College of Medicine, Nishinomiya, Japan. · Am J Gastroenterol. · Pubmed #15929771 No free full text.

Abstract: OBJECTIVE: Leukocytapheresis (LCAP) is a method of therapeutic apheresis that removes peripheral leukocytes. Previous studies showed that in patients with ulcerative colitis (UC), LCAP was more effective than high-dose steroid therapy, and it had few adverse effects. We investigated LCAP in a multicenter study using active and sham devices in a double-blind study in order to elucidate the placebo effect of extracorporeal treatment including anticoagulant medication. METHODS: Twenty-five patients with active UC of severe or moderately severe grade were enrolled and assigned to the active group or the sham group. Six patients were excluded from the study and 19 (10 in the active group and nine in the sham group) were evaluated. LCAP (treatment using an active device or a sham device) was performed once a week for 5 wk, followed by two additional sessions during the next 4 wk at 2-wk intervals. Steroids and other medications were continued at the same dosage for 4 wk, which included a 2-wk pre-observation period and the first 2 wk after the start of the LCAP treatment. New medications or increase in the dosage of previous medication were prohibited until evaluation was conducted. RESULTS: The clinical activity index (CAI) value of UC, indicated that the active group showed a significantly greater improvement (80%, 8/10) than the sham group (33%, 3/9; p<0.05). Adverse effects were observed in five patients (one in the active group and four in the sham group). None of these effects was severe and none of the sessions was terminated as a consequence of the adverse effects. CONCLUSION: The results confirmed that LCAP is a safe and effective therapeutic option for patients with active UC.

Naganuma M, Funakoshi S, Sakuraba A, Takagi H, Inoue N, Ogata H, Iwao Y, Ishi H, Hibi T. · Department of Internal Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan. · Inflamm Bowel Dis. · Pubmed #15290920 No free full text.

Abstract: BACKGROUND: Recently, granulocyte and monocyte adsorption apheresis (GCAP) has been shown to be safe and effective for active ulcerative colitis (UC). We analyzed the safety and efficacy of GCAP (G-1 Adacolumn) in patients with steroid-refractory and -dependent UC. G-1 Adacolumn is filled with cellulose acetate carriers that selectively adsorb granulocytes and monocytes/macrophages. METHODS: Forty-four patients with UC were treated with GCAP. These patients received 5 apheresis sessions over 4 weeks. Twenty patients had steroid-refractory UC (group 1) and 10 had steroid-dependent UC (group 2). Fourteen patients who did not want readministration of steroids were treated with GCAP at the time of relapse, just after discontinuation of steroid therapy (group 3). RESULTS: Of 44 patients treated with GCAP, 24 (55%) obtained remission (CAI < or = 4), 9 (20%) showed a clinical response, and 11 (25%) remained unchanged. Only 2 of 10 patients (20%) with severe steroid-refractory UC (CAI > or = 12) achieved remission, whereas 7 of 10 patients (70%) with moderate steroid-refractory UC achieved remission (p < 0.05). The dose of corticosteroids was tapered in 9 of 10 (90%) patients with steroid-dependent UC after GCAP therapy. Twelve (86%) of 14 patients in group 3 showed an improvement in symptoms and could avoid re-administration of steroids after GCAP. No severe adverse effects occurred. CONCLUSIONS: The findings of this study suggest that GCAP may be a useful alternative therapy for patients with moderate steroid-refractory or -dependent UC, although cyclosporin A or colectomy is necessary in patients with severe UC. GCAP may also be useful for avoiding re-administration of steroids at the time of relapse. Randomized, controlled clinical trials are needed to confirm these findings.

Kanauchi O, Mitsuyama K, Homma T, Takahama K, Fujiyama Y, Andoh A, Araki Y, Suga T, Hibi T, Naganuma M, Asakura H, Nakano H, Shimoyama T, Hida N, Haruma K, Koga H, Sata M, Tomiyasu N, Toyonaga A, Fukuda M, Kojima A, Bamba T. · Nutrient Food & Feed Division, Kirin Brewery Co. Ltd., Tokyo 104-8288, Japan. · Int J Mol Med. · Pubmed #14532996 No free full text.

Abstract: Germinated barley foodstuff (GBF), which mainly consists of dietary fiber and glutamine-rich protein, is a prebiotic for ulcerative colitis (UC). In our previous study, we carried out a clinical trial of GBF with mildly to moderately active UC patients and showed that GBF treatment was able to attenuate the symptoms of UC in a relatively short-term. The aim of this study was to investigate the efficacy of long-term administration of GBF in the treatment of UC in a multi-center open trial. Twenty-one patients with mildly to moderately active UC received 20-30 g of GBF for 24 weeks in an open-label protocol while baseline treatments (5-amino-salicyrate compounds and/or steroids) were continued. The response to the GBF treatment was evaluated using a clinical scoring and after 24 weeks of observation, the GBF group showed a significant decrease in clinical activity index (especially, the degree of visible blood in stools and the presence of nocturnal diarrhea) compared with the control group (p<0.05). No side effects related to GBF were observed. In conclusion, GBF can reduce the clinical activity of UC over long-term as well as short-term administration. Nutraceutical GBF therapy may have a place in long-term management of UC, but controlled studies are needed to demonstrate its efficacy in the treatment of this disorder.

Hibi T, Naganuma M, Kitahora T, Kinjyo F, Shimoyama T. · Center for the Research of Inflammatory Bowel Disease, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. · J Gastroenterol. · Pubmed #14505127 No free full text.

Abstract: BACKGROUND: 6-Mercaptopurine (6-MP) and azathioprine (AZA) have been used in patients with Crohn's disease (CD) and ulcerative colitis (UC) for reducing the dose of steroids and maintaining remission. However, some patients treated with 6-MP/AZA develop bone marrow suppression, one of the most serious side effects. The aim of this study was to evaluate the efficacy and safety of low-dose AZA (0.6-1.2 mg/kg per day) for maintaining remission in patients with UC. We also investigated the relationship between bone marrow suppression and thiopurine methyltransferase ( TPMT) mutation in the Japanese population. METHODS: Study 1. To investigate the frequency of TPMT mutation, findings for 82 patients among 141 patients with UC or CD who were treated with AZA or 6-MP were analyzed retrospectively. Polymerase chain reaction (PCR) methods were used to analyze allele mutations of the TPMT gene. Study 2. A multicenter prospective trial was performed. The subjects were 22 patients with UC with presence of remission for 3 months or more. They were treated with 50 mg/day of AZA, and we evaluated the remission rate at 6 months, adverse side effects, and changes in prednisone doses after the initiation of AZA. RESULTS: Study 1. Seventy-four (91%) of the 82 patients analyzed had no TPMT mutation, 7 (8%) had one mutant allele, and 1 (1%) had two mutant alleles. Of the total of 141 patients, 4 (44%) of the 9 patients who were treated with 50 mg/day of 6-MP or 100 mg/day of AZA developed bone marrow suppression, although no mutation of TPMT was seen in any of these patients. On the other hand, 8 (6%) of the 132 patients who were treated with 30 mg/day of 6-MP or 50 mg/day of AZA developed bone marrow suppression. Seven of 8 patients (88%) who developed bone marrow suppression with a low dose of AZA had a mutant TPMT allele. Study 2. In the 17 patients who could continue taking low-dose AZA for 6 months, 15 (88%) maintained remission. Of 8 patients treated with low-dose prednisone (5-10 mg/day), 3 patients (38%) could discontinue oral prednisone and 4 (50%) could reduce its dose. Six of the 22 patients (27%) had some adverse side effects. These side effects were ameliorated, or disappeared spontaneously, or disappeared with the discontinuation of AZA. CONCLUSIONS: A dose of 50 mg/day of AZA is effective and safe for maintenance of remission in the Japanese population. Investigation of the TPMT allele may be useful for predicting the appearance of bone marrow suppression, when low-dose 6-MP or AZA is given.

Kanauchi O, Suga T, Tochihara M, Hibi T, Naganuma M, Homma T, Asakura H, Nakano H, Takahama K, Fujiyama Y, Andoh A, Shimoyama T, Hida N, Haruma K, Koga H, Mitsuyama K, Sata M, Fukuda M, Kojima A, Bamba T. · Nutrient Food and Feed Division, Kirin Brewery, 10-1-2 Shinkawa, Chuo-ku, Tokyo 104-8288, Japan. · J Gastroenterol. · Pubmed #12572869 No free full text.

Abstract: BACKGROUND: Germinated barley foodstuff (GBF) is a prebiotic foodstuff that effectively increases luminal butyrate production by stimulating the growth of protective bacteria. In the first pilot study, GBF has been shown to reduce both clinical activity and mucosal inflammation in ulcerative colitis (UC). The aim of this study was to investigate the efficacy of GBF in the treatment of UC in a multicenter open control trial. METHODS: Eighteen patients with mildly to moderately active UC were divided into two groups using a random allocation protocol. The control group (n = 7) were given a baseline anti-inflammatory therapy for 4 weeks. In the GBF-treated group (n = 11), patients received 20-30 g GBF daily, together with the baseline treatment, for 4 weeks. The response to the treatments was evaluated clinically and endoscopically. Fecal microflora were also analyzed. RESULTS: After 4 weeks of observation, the GBF-treated group showed a significant decrease in clinical activity index scores compared with the control group (P < 0.05). No side effects related to GBF were observed. GBF therapy increased fecal concentrations of Bifidobacterium and Eubacterium limosum. CONCLUSIONS: Oral GBF therapy may have the potency to reduce clinical activity of UC. We believe that these results support the use of GBF administration as a new adjunct therapy for UC.

Sawada K, Muto T, Shimoyama T, Satomi M, Sawada T, Nagawa H, Hiwatashi N, Asakura H, Hibi T. · Dept of Gastroenterology, Hyogo College of Medicine, Nishinomiya, Tokyo, Japan. · Curr Pharm Des. · Pubmed #12570823 No free full text.

Abstract: The administration of steroids is not always effective for the treatment of ulcerative colitis (UC). Their long-term use often causes adverse effects which sometimes result in their stoppage and acute exacerbation. Therefore, an alternative treatment is necessary in order to decrease steroid dosage and avoid the clinical problems associated with steroids. Methods The effectiveness and adverse effects of a leukocytapheresis (LCAP) were investigated in a controlled multicenter trial with randomized assignment of 76 active-stage UC patients in two groups. In the LCAP group (39 patients), LCAP weekly for 5 weeks as an intensive therapy was added to the on-going drug therapy, while steroids were maintained but not increased, and then LCAP was gradually reduced to once every 4 weeks as a maintenance therapy. In the high dose prednisolone (h-PSL) group (37 patients), PSL was added or increased 30 approximately 40 mg/day for moderately severe and 60 approximately 80 mg/day for severe patients and then gradually tapered. Findings The LCAP group showed a significantly higher effectiveness (74% vs. 38%; p=0.005) and lower incidence of adverse effects (24% vs. 68%; p<0.001). The patients were able to continue the trial for a longer period in the LCAP group than the h-PSL group (p=0.012). Clinical activity and endoscopic indexes showed the LCAP group had better improvements than the h-PSL group. Interpretation The results of the trial show that LCAP permits a reduction in total PSL dosage and is more effective and safer than high-dose PSL administration for intensive therapy, and LCAP may maintain remission longer than PSL.

Naganuma M, Iizuka B, Torii A, Ogihara T, Kawamura Y, Ichinose M, Kojima Y, Hibi T, Anonymous00251. · School of Medicine, Keio University; School of Medicine, Tokyo Women's Medical University, Japan. · Am J Gastroenterol. · Pubmed #11316158 No free full text.

Abstract: OBJECTIVES: Studies in the US and Europe have shown that appendectomy may prevent the development of ulcerative colitis, but no detailed study has been conducted in Japan, where ulcerative colitis is uncommon and the population is racially homogeneous. In addition, there has been no detailed analysis of the relationship between appendectomy and the clinical course of ulcerative colitis. In this multicenter clinical study, we evaluated the effects of appendectomy on ulcerative colitis in Japan. METHODS: A case-control study was undertaken in seven medical institutions comparing the incidence of appendectomy and tonsillectomy in 325 patients with ulcerative colitis and 325 controls matched for age (10-yr intervals) and sex. Disease duration, extent, and prognosis were determined in 21 patients with ulcerative colitis who underwent appendectomies and 304 patients with ulcerative colitis who did not undergo appendectomies. RESULTS: Appendectomy was performed in a significantly lower percentage of patients in the ulcerative colitis group (21/325, 6.5%) than in the control group (53/325, 16.3%) (p < 0.001) (odds ratios = 0.355, 95% CI = 0.208-0.603). In contrast, no significant difference was observed between the groups with respect to tonsillectomy. The mean age (25.7 +/- 10.9 yr) of patients with ulcerative colitis at the time of appendectomy was significantly higher than the mean age (20.1 +/- 8.7 yr) of patients in the control group at the time of appendectomy (p < 0.05). The incidence of proctitis was higher in the appendectomy group than in the group that did not undergo appendectomies (38.1% vs 18.1%). In addition, the recurrence rates were significantly lower in the appenectomy group than in the group that did not undergo appendectomies (57. 1% vs 78.6%, p < 0.05), although both groups were similar in composition as to sex, age, duration of disease, smoking status, and previous medical treatment. CONCLUSIONS: Our results indicate that appendectomy has a negative association with and perhaps a preventive effect on the development of ulcerative colitis in the Japanese population. Furthermore, appendectomy also appears to reduce the extent and recurrence of ulcerative colitis.

Naganuma M, Hibi T. · Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Keio University. · Nippon Shokakibyo Gakkai Zasshi. · Pubmed #19578305 No free full text.

This publication has no abstract.

Hisamatsu T, Hibi T. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University. · Nihon Rinsho Meneki Gakkai Kaishi. · Pubmed #19564713 links to  free full text

Abstract: Recent advance of molecular biology and immunology contributes to the development biologics such as anti-TNFalpha agent in the treatment for inflammatory bowel disease (IBD). Although therapeutic strategy of IBD has not been changed for a long time, success of Infliximab, first anti-TNFalpha agent, now changes therapeutic strategy of IBD dramatically. Top-down strategy has been considered to improve patients' natural history in the therapy for Crohn's disease as well as in rheumatoid arthritis. Infliximab also has been expected as a promising medicine for pediatric Crohn's disease. Furthermore, Infliximab has been approved for the therapy of ulcerative colitis. These tremendous successes of Infliximab have encouraged us to develop other anti-TNF agents and other biologics. In this review, we describe current topics of biologics in IBD treatment and discuss future direction.

Kanai T, Nemoto Y, Kamada N, Totsuka T, Hisamatsu T, Watanabe M, Hibi T. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. · Curr Opin Gastroenterol. · Pubmed #19448533 No free full text.

Abstract: PURPOSE OF REVIEW: This review focuses on CD4+ T cells involved in the mediation of inflammatory tissue damage in murine models of inflammatory bowel diseases (IBDs). In particular, we describe the distinct roles of the homeostatic cytokine IL-7, which is essential to the maintenance of colitogenic memory CD4+ cells, and the newly discovered effector cytokine IL-17. We also discuss the close correlation between colitogenic Th17-type CD4+ T cells and inducible CD4+CD25+Foxp3+ regulatory T cells. RECENT FINDINGS: IBDs are characterized by wasting and chronic intestinal inflammation induced by many different cytokine-mediated pathways. It is clearly recognized that medical and surgical interventions do not cure Crohn's disease because relapse is the rule after remission. Until a few years ago, IBD was classified into Th1-dependent, that is, Crohn's disease, and Th2-dependent, that is, ulcerative colitis, phenotypes. However, in recent years, it has been shown that new T-cell subclasses, that is, Th17 and regulatory T cells (T(R)), exist independently of Th1 and Th2 and that they play a central role in modulating IBD. SUMMARY: The persistence of IL-7-dependent colitogenic memory CD4+ T cells is critical to the maintenance of experimental colitis. On the other hand, though Th1 and Th2 colitogenic memory CD4+ cells exist, in recent years the central role of IL-17-producing Th17-type cells in IBD has attracted renewed interest. The development of molecularly targeted therapies aimed at a variety of different Th-dependent pathogenic mechanisms may represent a novel approach to IBD therapy.

Asakura K, Nishiwaki Y, Inoue N, Hibi T, Watanabe M, Takebayashi T. · Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan, · J Gastroenterol. · Pubmed #19424654 No free full text.

Abstract: PURPOSE: The prevalence of inflammatory bowel diseases is much lower in Asian countries, including Japan, than in Western countries, but it is rapidly increasing. However, no recent reports describe the current prevalence of these diseases in Japan, so we performed a descriptive epidemiological study to remedy this situation and to elucidate various characteristics of inflammatory bowel diseases in this country. METHODS: Japan has a nationwide registration system of patients with intractable diseases, including ulcerative colitis and Crohn's disease. To calculate the age-standardized prevalence, we used this registration system to collect patient data, and we obtained detailed population data from the Japanese government's population estimates made in 2003 and 2004 and from the 2005 population census. In addition, information about the characteristics of ulcerative colitis and Crohn's disease patients was collected through the registration system. RESULTS: The age-standardized prevalence of ulcerative colitis in Japan in 2005 was 63.6 per 100,000 persons, and that of Crohn's disease was 21.2. Patient numbers have been steadily increasing with time. The age distribution was found to differ between the two diseases, with Crohn's disease affecting mainly younger people. In both diseases, more than 50% of the patients were male, and over 80% of the patients were classified as mild to moderate in terms of severity. CONCLUSIONS: The prevalence of inflammatory bowel diseases in Japan is still much lower than in Western countries. Surveillance should be continued, and research to clarify their etiologies in association with the increasing number of patients in Japan is needed.