Interleukin 12/interleukin 23 pathway: Biological basis and therapeutic effect in patients with Crohn's disease

Αγγελετοπούλου, Ιωάννα; Assimakopoulos, Stelios F.; Konstantakis, Christos; Triantos, Christos

doi:10.3748/wjg.v24.i36.4093

Cited by 43 publications

(34 citation statements)

References 78 publications

(100 reference statements)

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“…6). The monoclonal antibody ustekinumab directed against a common subunit of interleukin 12 and interleukin 23 interferes with the binding of these cytokines with the IL-12 receptor to inhibit inflammatory signalling 30 . Ustekinumab has European marketing authorisation for the treatment of psoriasis and Crohn's disease (CD) after demonstrating efficacy in clinical trials 31 , and is under evaluation for ulcerative colitis (UC).…”

Section: Pcsk9mentioning

confidence: 99%

Genetic drug target validation using Mendelian randomisation

et al. 2020

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Mendelian randomisation (MR) analysis is an important tool to elucidate the causal relevance of environmental and biological risk factors for disease. However, causal inference is undermined if genetic variants used to instrument a risk factor also influence alternative disease-pathways (horizontal pleiotropy). Here we report how the 'no horizontal pleiotropy assumption' is strengthened when proteins are the risk factors of interest. Proteins are typically the proximal effectors of biological processes encoded in the genome. Moreover, proteins are the targets of most medicines, so MR studies of drug targets are becoming a fundamental tool in drug development. To enable such studies, we introduce a mathematical framework that contrasts MR analysis of proteins with that of risk factors located more distally in the causal chain from gene to disease. We illustrate key model decisions and introduce an analytical framework for maximising power and evaluating the robustness of analyses.

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Section: Pcsk9mentioning

confidence: 99%

Genetic drug target validation using Mendelian randomisation

et al. 2020

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“…Полагаем, что провоспалительные цитокины в первые сутки после повреждения вызывают демаргинацию пристеночного пула нейтрофилов, выход зрелых нейтрофилов из костного мозга, а также активацию циркулирующих в крови нейтрофилов. Это было [10,27,32]. Помимо активации Th17-зависимых реакций, IL-23 участвует в активации лимфоидных клеток врожденного иммунитета (ILCs), CD8 + , NK-, NKT-клеток [16,26,32].…”

Section: Discussionunclassified

Immunotropic effects of Curcuma longa extract as a component of original rectal suppositories in the dynamics of experimental Сrohn’s disease

et al. 2020

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Crohn’s disease is an urgent problem of modern gastroenterology due to increasing prevalence, severity of complications and side effects of the basic therapy, in particular upon treatment with 5-aminosalicylic acid (5-ASA). Searching, development and trials of new effective drugs with minimal side effects in Crohn’s disease is an urgent task. Curcuma longa is one of the initial substances containing curcumin with antioxidant, cytoprotective, anti-inflammatory properties. Its effectiveness has been demonstrated in few studies with its systemic use in Crohn’s disease treatment. Our aim was to perform a comparative analysis of curcumin and 5-ASA effect applied as a composition of rectal suppositories, studying clinical signs and indices of immune status in experimental Crohn’s disease. The study was performed on 70 Wistar male rats. Crohn’s disease was modeled by introduction of a 50% alcohol solution of trinitrobenzene sulfonic acid (TNBS) per rectum, and verified by clinical and morphological methods. Rectal suppositories, each containing 50 mg of 5-ASA and original suppositories containing 0.075 mg of curcumin were used over 12 hours during 7 days. The studies were performed on the 3rd , 5th and 7th days of Crohn’s disease.In the course of experimental TNBS-induced Crohn’s disease in animals, an increased frequency of bowel motility, appearance of blood in the stool, decreased body weight progressed from the 3rd to the 7th days of observation, along with increased number in CD3+, CD45RA+ lymphocytes in blood, higher number of segmented neutrophils, lower absorption and NBT-reducing activity of blood neutrophils, increased serum concentrations of IL-23, IgM, IgG. Composition of the new medication form was justified; production technology and standardization of the suppositories containing curcumin for the treatment for Crohn’s disease were developed. Usage of rectal suppositories with curcumin is associated with decreased severity of clinical signs, decrease and partial restoration of segmented neutrophils, CD3+ lymphocyte numbers in blood, recovery of absorption and NBT-reducing ability of blood neutrophils, and decrease of IL-23, IgM, IgG concentrations in serum. The effectiveness of rectal suppositories with curcumin is compared to the effectiveness of the use of rectal suppositories with 5-ASA in terms of disease activity index, the number of neutrophils and CD3+ lymphocytes in the blood, serum concentrations of IL-23, IgM and IgG, in, at lesser extent, in terms of absorption and NBT- reducing ability of blood neutrophils.The composition and production technology of rectal suppositories with curcuminwas developed; the leukocyte populations, CD3+, CD45RA+ lymphocytesin blood were assesed, neutrophil absorption and NBT-reducing ability, IL-23, IgM and IgG concentrations were determined; the use of rectal suppositories with curcumin in experimental Crohn’s disease is comparable with the effectiveness of rectal suppositories with 5-ASA.

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“…It is an (interleukin) IL-12 and IL-23 antagonist. It is used in patients with moderate to severe CD who have failed treatment with corticosteroids or immunosuppressants [24]. The adverse effects of using ustekinumab are anaphylactic reactions, diarrhea, upper respiratory tract infections, and injection site reactions [19,24].…”

Section: Ustekinumabmentioning

confidence: 99%

“…Ustekinumab is used to treat moderate-to-severe CD patients who have previously failed treatment on steroids, AZA/6-MP, methotrexate, or anti-TNF agents. It is also used in patients naive to anti-TNF agents [19,24].…”

Section: Agents Targeting Il-12/23 (Anti-p40 Antibody)mentioning

confidence: 99%

Medical Management of Crohn's Disease

Gade

Douthit

Townsley

2020

Cureus

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Crohn's disease (CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract from the mouth to the anus, sparing the rectum. The goal of medical therapy is to induce remission with medications, followed by the administration of maintenance medications to prevent a relapse of the disease. The concept of induction of remission and maintenance of remission is very important, as there is an overlap of medications used to induce and maintain remission. Physicians first direct treatment to induce a remission that involves relief of symptoms and mucosal healing of the lining of the colon and then provide long-term treatment to maintain the remission. Standard treatment for CD depends on the extent of involvement and disease severity, for example, mild, moderate, severe, and fulminant.

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Interleukin 12/interleukin 23 pathway: Biological basis and therapeutic effect in patients with Crohn's disease

Cited by 43 publications

References 78 publications

Genetic drug target validation using Mendelian randomisation

Genetic drug target validation using Mendelian randomisation

Immunotropic effects of Curcuma longa extract as a component of original rectal suppositories in the dynamics of experimental Сrohn’s disease

Medical Management of Crohn's Disease

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