Biologic therapy of inflammatory bowel disease

Sandborn, William J.; Targan, Stephan R.

doi:10.1053/gast.2002.33426

Cited by 296 publications

(216 citation statements)

References 125 publications

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“…suppressive, drugs (36,37). However, these treatments do not modify the disease course, but only alleviate the symptoms while inducing severe side effects that limit their use.…”

Section: The Effect Of Ga On Ibdsmentioning

confidence: 99%

Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications

Arnon

Aharoni

2004

Proc. Natl. Acad. Sci. U.S.A.

174

131

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Glatiramer acetate (GA, Copaxone, Copolymer 1) is an approved drug for the treatment of multiple sclerosis and is highly effective in the suppression of experimental autoimmune encephalomyelitis in various species. The mode of action of GA is by initial strong promiscuous binding to MHC molecules and consequent competition with various myelin antigens for their presentation to T cells. A further aspect of its action is potent induction of specific suppressor cells of the T helper 2 (Th2) type that migrate to the brain and lead to in situ bystander suppression. Furthermore, the GA-specific cells in the brain express the antiinflammatory cytokines IL-10 and transforming growth factor ␤, in addition to brain-derived neurotrophic factor, whereas they do not express IFN-␥. Based on this immunomodulatory mode of action, we explored the potential of GA for two other applications: prevention of graft rejection and amelioration of inflammatory bowel diseases. GA was effective in amelioration of graft rejection in two systems by prolongation of skin graft survival and inhibition of functional deterioration of thyroid grafts, across minor and major histocompatibility barriers. In all transplantation systems GA treatment inhibited the detrimental secretion of Th1 inflammatory cytokines and induced beneficial Th2͞3 antiinflammatory response. GA was effective also in combination with low-dose immunosuppressive drugs. Inflammatory bowel diseases are characterized by detrimental imbalanced proinflammatory immune reactivity in the gut. GA significantly suppressed the various manifestations of trinitrobenzene sulfonic acid-induced colitis, including mortality, weight loss, and macroscopic and microscopic colonic damage. GA suppressed local lymphocyte proliferations and tumor necrosis factor ␣ detrimental secretion but induced transforming growth factor ␤, thus confirming the involvement of Th1 to Th2 shift in GA mode of action.

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“…suppressive, drugs (36,37). However, these treatments do not modify the disease course, but only alleviate the symptoms while inducing severe side effects that limit their use.…”

Section: The Effect Of Ga On Ibdsmentioning

confidence: 99%

Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications

Arnon

Aharoni

2004

Proc. Natl. Acad. Sci. U.S.A.

174

131

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“…During the past years, the spectrum of therapeutic options has been broadened by the introduction of various biological agents. 3 However, there are rare cases of patients with CD, in whom current medical and surgical therapy cannot lead to a continuing remission.…”

mentioning

confidence: 99%

Complete remission of Crohn's disease after high-dose cyclophosphamide and autologous stem cell transplantation

Kreisel

Potthoff

Bertz

et al. 2003

Bone Marrow Transplant

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Summary:In a 36-year-old male with ileocolic Crohn's disease (CD) no long-lasting remission was obtained by treatment with corticosteroids, mesalazine, azathioprine and antibiotics. Surgical interventions due to relapsing fistulae and abscesses resulted in the removal of 41.5 m of small bowel and left only 40 cm of large bowel. In July 2000, a new fistula and abscess developed. The combination of corticosteroids, mesalazine, ciprofloxacin, metronidazol, azathioprine, formula diet and anti-TNF-a antibody largely reduced clinical activity, and resection of fistula and abscess were successful. Despite clinical remission, histology showed activity in the small bowel and the colon. In March 2001, stem cell mobilization chemotherapy with cyclophosphamide was performed. It induced an endoscopic remission for 9 months, which was maintained on azathioprine and corticosteroids. After relapse, in March 2002, high-dose chemotherapy with cyclophosphamide and reinfusion of T-cell-depleted autologous peripheral CD34+ blood stem cells were performed. This led to a complete clinical, endoscopical and histological remission for 9 months without any treatment. Thereafter, endoscopy showed initial aphthous lesions with minimal histological signs of inflammation. The patient is asymptomatic, but low-dose prednisolone and methotrexate are prophylactically given. Immunoablative chemotherapy followed by autologous peripheral blood stem cell transplantation may be a beneficial therapeutic option in complicated refractory CD.

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“…In cases when cytokine are directly applied, it leads to low bioavailability due to the injection of protein, and it may lead to occurrence of problems such as low pharmacokinetic and chemical instability as well as inducement of immune response [45]. Currently, as active researches are taking place about etiology of inflammatory bowel disease, cytokine and cells related to the Crohn's disease and ulcerative colitis are being identified continually, and numerous biological medicine which selectively attacks specific molecules or routes related to the intestinal inflammation have been developed [64,66]. Accordingly, necessity in the cytokine gene therapy is being suggested for inflammatory bowel disease, and attention is being focused in the application [45].…”

Section: Proinflammatory Cytokinementioning

confidence: 99%

Inflammatory Bowel Disease and Cytokine

Choi¹,

Cho²,

Choi³

2013

Journal of Life Science

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Inflammatory bowel disease, known as Crohn's disease and ulcerative colitis, is an unexplained disease characterized by chronic inflammation that repeats a cycle of relapse, improvement, and complications. The cause of inflammatory bowel disease is not clearly known, but it is predicted that a complex of various factors precipitate its occurrence. In particular, inflammatory mediators, such as cytokine, induce an increase in cell-mediated inflammatory responses. Focal tissue damage then occurs in the intestinal mucosa because of the weakening of the immune-modulating functions of cotton. Immune and inflammatory responses do not decrease appropriately but continue until they lead to chronic inflammation. Current research has focused on the cytokine genes, which have important roles in these inflammatory responses. Cytokine is a glycoprotein that is produced mostly in activated immune cells. It connects the activation, multiplication, and differentiation between immune cells, which causes focal tissue damage and inflammatory response. Moreover, butyrate, which originates in dietary fiber and plays an important role in the structure and function of the intestinal area, shows control functions in the intestinal immune system by decreasing the proinflammatory cytokine and increasing the anti-inflammatory cytokine. Therefore, this research investigated the molecular mechanism of the anti-inflammatory effects of butyrate to comprehend the cytokine controlling abilities of butyrate in the immune cells. Butyrate is expected to have potential in new treatment strategies for inflammatory bowel disease.

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Biologic therapy of inflammatory bowel disease

Cited by 296 publications

References 125 publications

Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications

Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications

Complete remission of Crohn's disease after high-dose cyclophosphamide and autologous stem cell transplantation

Inflammatory Bowel Disease and Cytokine

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