New pathophysiological insights and modern treatment of IBD

Engel, Matthias; Neurath, Markus F.

doi:10.1007/s00535-010-0219-3

Cited by 171 publications

(142 citation statements)

References 156 publications

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“…However, their use may result in severe side effects and complications, such as an increased rate of malignancies or infectious diseases [5,15]. For many years there have been numerous efforts to find a new effective method that would allow controlling specifically unwanted immune responses that occur during autoimmune reaction.…”

Section: Introductionmentioning

confidence: 99%

Epicutaneous immunization with protein antigen TNP-Ig alleviates TNBS-induced colitis in mice

Majewska‐Szczepanik

Góralska

Marcińska

et al. 2012

Pharmacological Reports

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Abstract:Background: Ulcerative colitis (UC) is a chronic inflammatory autoimmune disease with limited treatment modalities. The animal model of colitis induced by treatment with trinitrobenzene sulfonic acid (TNBS-colitis) is commonly used to test new therapies of this disease. In our previous work we found that epicutaneous (EC) immunization with protein antigen induced a state of profound immunosuppression that inhibited inflammatory response in contact sensitivity, in experimental autoimmune encephalomyelitis (EAE) and in allogeneic skin graft rejection. Methods: TNBS-induced colitis was used as an experimental model. Results: In our current work, we showed that EC immunization with TNP-conjugated mouse immunoglobulin (TNP-Ig) prior to induction of TNBS-colitis alleviates disease severity what was determined by the body weight, the length and the weight of the colon, the histological activity index (HAI) and myeloperoxidase activity (MPO). Observed amelioration of the disease in TNP-Ig patched mice was accompanied with decreased production of IFN-g and IL-17A by splenocytes. Additionally, spleen cells isolated from mice EC immunized with TNP-Ig prior to colitis induction showed increased production of IL-10 suggesting that this cytokine might be involved in inhibiting inflammatory response in the colon. Conclusion: This work shows that EC immunization with protein antigen prior to TNBS-colitis induction ameliorates disease and observed suppression of inflammatory response in the colon might be mediated by IL-10.

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Section: Introductionmentioning

confidence: 99%

Epicutaneous immunization with protein antigen TNP-Ig alleviates TNBS-induced colitis in mice

Majewska‐Szczepanik

Góralska

Marcińska

et al. 2012

Pharmacological Reports

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“…The inflammatory pattern in CD has been associated with enhanced occurrence of T-helper (Th)1 and Th17 cells, while the T-cell signature of UC is more similar to a Th2 cell disease type [1,10]. The development of Th1 and Th17 cells in CD is triggered by inflammatory mediators, such as IL-12, IL-18, IL-23 and TGFβ that are secreted by antigen presenting cells (APC) and macrophages [11].…”

Section: Cytokines As Drug Targets In Ibdmentioning

confidence: 99%

Review: New Anti-Cytokines for IBD: What is in the Pipeline?

Scharl

Vavricka²,

Rogler

2013

CDT

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Significant advances have been achieved in the understanding of the pathogenesis of inflammatory bowel disease (IBD). A number of susceptibility genes have been detected by large genome wide screening-approaches. New therapeutic concepts emerge from these insights. The most important progress in recent years certainly is the introduction of biologics in the therapy of IBD. TNF blockers have been shown to be very effective for the control of complicated disease courses. Currently, in addition to the three already established anti-TNF antibodies, new anti-TNF molecules, for example Golimumab, are in clinical trials and also reveal promising results. However, not all of the patients respond to anti-TNF treatment and many patients lose their response. Therefore, additional therapeutic approaches are urgently needed. Attractive therapy targets are cytokines as well as their receptors and signaling pathways. At the moment a large number of biologicals and inhibitors are tested in clinical trials and some of them provide very promising results for the treatment of IBD patients. In particular, inhibition of IL-12p40 by specific antibodies as well as of the janus kinase (JAK)3 by a small molecule promise to be very effective approaches. Though antibodies targeting for example IL-6, IL-6R, IL-13 or CCR9 are only in the early steps of clinical development, they have already demonstrated to be a possible treatment option which needs to be confirmed in further trials. Taken together a large number of new therapeutic anti-cytokine approaches are currently tested in clinical trials in IBD patients. In this review, the new therapeutic approaches for cytokine inhibition in IBD patients are discussed. Taken together a large number of new therapeutic anti-cytokine approaches are currently tested in clinical trials in IBD patients. In this review, the new therapeutic approaches for cytokine inhibition in IBD patients are discussed.

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“…Existing therapies for symptomatic relief of IBD include anti-inflammatory drugs, immunosuppressants, biologic agents, antibiotics, and aminosalicylic acid (5-ASA) based drugs. However, these treatments are not entirely satisfactory due to limited effectiveness and associated side effects [3][4][5][6] . Thus there is a need to identify drugs that provide safer, convenient and efficient means of therapeutic intervention for IBD.…”

Section: Introductionmentioning

confidence: 99%