Interleukin-12 Antagonists as New Therapeutic Agents in Inflammatory Bowel Disease

Pathobiology ◽  
2002 ◽  
Vol 70 (3) ◽  
pp. 177-183 ◽  
Author(s):  
Carsten Schmidt ◽  
Thomas Marth ◽  
Bianca M. Wittig ◽  
Andreas Hombach ◽  
Hinrich Abken ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Therapeutic Agents ◽  
Interleukin 12 ◽  
Inflammatory Bowel

scholarly journals Controlling Gut Inflammation by Restoring Anti-Inflammatory Pathways in Inflammatory Bowel Disease

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 397 ◽  
Author(s):  
Paolo Giuffrida ◽  
Sara Cococcia ◽  
Mariangela Delliponti ◽  
Marco Vincenzo Lenti ◽  
Antonio Di Sabatino
Keyword(s):  
Inflammatory Bowel Disease ◽  
Side Effects ◽  
Bowel Disease ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Interleukin 12 ◽  
Inflammatory Pathways ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Inflammatory bowel disease (IBD) is caused by a dysregulated immune response against normal components of the intestinal microflora combined with defective functioning of anti-inflammatory pathways. Currently, all therapies approved for IBD manipulate the immune system by inhibiting pro-inflammatory mechanisms, such as tumor necrosis factor-α, gut-homing α4β7 integrin, interleukin-12/interleukin-23, and Janus kinases. However, some IBD patients are non-responders to these drugs, which are also associated with serious side effects. Thus, it has been hypothesized that therapies aimed at restoring anti-inflammatory signals, by exploiting the tolerogenic potential of cytokines (interleukin-10, transforming growth factor-β, granulocyte macrophage colony-stimulating factor), immune cells (regulatory T cells, tolerogenic dendritic cells), or mesenchymal stem cells, might offer promising results in terms of clinical efficacy with fewer side effects. In this review, we provide new insights into putative novel treatments aimed at restoring anti-inflammatory signaling pathways in IBD.

scholarly journals Emerging treatments for inflammatory bowel disease

2020 ◽  
Vol 11 ◽  
pp. 204062231989929 ◽  
Author(s):  
Karl Hazel ◽  
Anthony O’Connor
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Severe Disease ◽  
Treatment Options ◽  
Response To Therapy ◽  
Interleukin 12 ◽  
Cell Transplant ◽  
Faecal Microbiota ◽  
Emerging Treatments ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation, a relapsing and remitting clinical course, requirement for lifelong medication and often, significant morbidity. While multiple effective therapeutic options exist for the treatment of IBD, a proportion of patients will either fail to respond or lose response to therapy. Advances in therapeutics, such as the gut-specific anti-integrins, now offer patients an alternative option to systemic immunosuppression. Anti-interleukin 12 (anti-IL-12)/IL-23 agents offer new and effective treatment options for CD, while the oral small molecules now offer an oral alternative for the treatment of moderate-to-severe disease, previously requiring subcutaneous injection or intravenous infusion. Alternatives to pharmacological treatment such as stem-cell transplant and faecal microbiota transplant are also showing some promise in the treatment of both CD and UC.

The Role of Immune and Epithelial Stem Cells in Inflammatory Bowel Disease Therapy

2020 ◽  
Vol 21 (14) ◽  
pp. 1405-1416 ◽  
Author(s):  
Agata Binienda ◽  
Sylwia Ziolkowska ◽  
Ingvild H. Hauge ◽  
Maciej Salaga
Keyword(s):  
Inflammatory Bowel Disease ◽  
Stem Cells ◽  
Bowel Disease ◽  
Lymphoid Cells ◽  
Interleukin 12 ◽  
Epithelial Stem Cells ◽  
Significant Deterioration ◽  
Hematopoietic Stem ◽  
Inflammatory Bowel

Background: Inflammatory Bowel Disease (IBD) is categorized as Crohn’s disease (CD) and Ulcerative colitis (UC) and is characterized by chronic inflammation in the gastrointestinal (GI) tract. Relapsing symptoms, including abdominal pain, increased stool frequency, loss of appetite as well as anemia contribute to significant deterioration of quality of life. IBD treatment encompasses chemotherapy (e.g. corticosteroids, thiopurines) and biological agents (e.g. antibodies targeting tumour necrosis factor α, interleukin 12/23) and surgery. However, efficacy of these therapies is not satisfactory. Thus, scientists are looking for new options in IBD treatment that could induce and maintain remission. Objective: To summarize previous knowledge about role of different intestinal cells in IBD pathophysiology and application of stem cells in the IBD treatment. Results: Recent studies have emphasized an important role of innate lymphoid cells (ILCs) as well as intestinal epithelial cells (IECs) in the IBD pathophysiology suggesting that these types of cells can be new targets for IBD treatment. Moreover, last studies show that stem cells transplantation reduces inflammation in patients suffering from IBD, which are resistant to conventional therapies. Conclusion: Both hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are able to restore damaged tissue and regulate the immune system. Autologous HSCs transplantation eliminates autoreactive cells and replace them with new T-cells resulting a long-time remission. Whereas MSCs transplantation is effective therapy in one of the major complications of IBD, perianal fistulas.

scholarly journals Drugs as causative agents and therapeutic agents in inflammatory bowel disease

2013 ◽  
Vol 3 (5) ◽  
pp. 289-296 ◽  
Author(s):  
Phani Krishna Kondamudi ◽  
Rajkumar Malayandi ◽  
Chandramohan Eaga ◽  
Deepika Aggarwal
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Therapeutic Agents ◽  
Causative Agents ◽  
Inflammatory Bowel

scholarly journals Sphingolipids as Mediators in the Crosstalk between Microbiota and Intestinal Cells: Implications for Inflammatory Bowel Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Phillips-Farfán Bryan ◽  
Carvajal Karla ◽  
Medina-Torres Edgar Alejandro ◽  
Espinosa-Padilla Sara Elva ◽  
Fabrias Gemma ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Response ◽  
Immune System ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Therapeutic Agents ◽  
Intestinal Cells ◽  
Intestinal Immunity ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) describes different illnesses characterized by chronic inflammation of the gastrointestinal tract. Although the pathogenic mechanisms leading to IBD are poorly understood, immune system disturbances likely underlie its development. Sphingolipids (SLs) have been identified as important players and promising therapeutic targets to control inflammation in IBD. Interestingly, it seems that microorganisms of the normal gut microbiota and probiotics are involved in sphingolipid function. However, there is a great need to investigate the role of SLs as intermediates in the crosstalk between intestinal immunity and microorganisms. This review focuses on recent investigations that describe some mechanisms involved in the regulation of cytokine profiles by SLs. We also describe the importance of gut microbiota in providing signaling molecules that favor the communication between resident bacteria and intestinal cells. This, in turn, modulates the immune response in the bowel and likely in other peripheral organs. The potential of SLs and gut microbiota as targets or therapeutic agents for IBD is also discussed.

scholarly journals Genetic Dissection of the Cellular Pathways and Signaling Mechanisms in Modeled Tumor Necrosis Factor–induced Crohn's-like Inflammatory Bowel Disease

2002 ◽  
Vol 196 (12) ◽  
pp. 1563-1574 ◽  
Author(s):  
Dimitris Kontoyiannis ◽  
George Boulougouris ◽  
Menelaos Manoloukos ◽  
Maria Armaka ◽  
Maria Apostolaki ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bone Marrow ◽  
Tumor Necrosis Factor ◽  
Bowel Disease ◽  
Tumor Necrosis ◽  
Interleukin 12 ◽  
Intestinal Pathology ◽  
Inflammatory Bowel ◽  
Cellular Pathways ◽  
Necrosis Factor

Recent clinical evidence demonstrated the importance of tumor necrosis factor (TNF) in the development of Crohn's disease. A mouse model for this pathology has previously been established by engineering defects in the translational control of TNF mRNA (TnfΔAREmouse). Here, we show that development of intestinal pathology in this model depends on Th1-like cytokines such as interleukin 12 and interferon γ and requires the function of CD8+ T lymphocytes. Tissue-specific activation of the mutant TNF allele by Cre/loxP-mediated recombination indicated that either myeloid- or T cell–derived TNF can exhibit full pathogenic capacity. Moreover, reciprocal bone marrow transplantation experiments using TNF receptor–deficient mice revealed that TNF signals are equally pathogenic when directed independently to either bone marrow–derived or tissue stroma cell targets. Interestingly, TNF-mediated intestinal pathology was exacerbated in the absence of MAPKAP kinase 2, yet strongly attenuated in a Cot/Tpl2 or JNK2 kinase–deficient genetic background. Our data establish the existence of redundant cellular pathways operating downstream of TNF in inflammatory bowel disease, and demonstrate the therapeutic potential of selective kinase blockade in TNF-mediated intestinal pathology.

scholarly journals The Era of Janus Kinase Inhibitors for Inflammatory Bowel Disease Treatment

2021 ◽  
Vol 22 (21) ◽  
pp. 11322
Author(s):  
Jin-Woo Kim ◽  
Su-Young Kim
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Kinase Inhibitors ◽  
Significant Proportion ◽  
Janus Kinase ◽  
Response To Treatment ◽  
Interleukin 12 ◽  
Disease Treatment ◽  
Janus Kinase Inhibitors ◽  
Inflammatory Bowel

For a significant proportion of patients with inflammatory bowel disease (IBD), primary non-response and secondary loss of response to treatment remain significant issues. Anti-tumor necrosis factor therapies have been licensed for use in IBD. Other disease-related pathways have been targeted as well, including the interleukin 12/23 axis and lymphocyte tracking. However, the need for parenteral administration and the associated costs of dispensing and monitoring all biologics remain a burden on healthcare systems and patients. Janus kinase inhibitors are small-molecule drugs that can be administered orally and are relatively inexpensive, thus offering an additional option for treating IBD. They have been shown to be effective in patients with ulcerative colitis (UC), but they are less effective in those with Crohn’s disease (CD). Nonetheless, given the immune-system-based mechanism of these drugs, their safety profile remains a cause for concern. This article provides an overview of Janus kinase (JAK) inhibitors and new trends in the treatment of IBD.

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