scholarly journals The Crohn’s Disease and Proinflammatory Cytokines

2021 ◽  
Author(s):  
Ahmed Al Qteishat ◽  
Kiril Kirov ◽  
Dmitry O. Bokov
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Proinflammatory Cytokines ◽  
Activity Index ◽  
Systemic Reaction ◽  
The Body ◽  
Healthy People ◽  
Control Group ◽  
Tnf Α ◽  
Ifn Γ

Abstract The aim of the study was to examine the profile of the main proinflammatory cytokines in the serum of patients with Crohn's disease and establish their association with the severity and activity of the disease. A total of 61 patients (29 women (47.5%), 32 men (52.5%) aged from 18 to 40 years (mean age (30.42 ± 2.51) years) with the verified diagnosis of Crohn's disease in the active phase were examined. The control group consisted of 30 virtually healthy people (VHP) of corresponding age. Crohn's disease is characterized by reliable (p<0.05) increase of pro-inflammatory cytokines in blood compared to virtually healthy people: TNF-α – by 4.45 times (p<0.05), IL-1α – by 5.08 times (p<0.05), IL-6 – by 2.16 times (p<0.05), IL-8 – by 2.04 times (p<0.05), and IFN-γ – by 5.30 times (p<0.05), which can be due to the development of the active inflammatory process in the intestine and the systemic reaction of the body. The degree of increase in TNF-α and IFN-γ content, as well as the presence of direct correlations between the Best activity index and the content of these cytokines in the blood of the examined patients, confirm their leading role in the cascade of immune-inflammatory reactions during Crohn's disease.

scholarly journals P187 The significance of netrin-1 level in the clinical activity of ulcerative colitis, its association between TNF-α and IL-6

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S232-S232
Author(s):  
H Korkmaz ◽  
K Fidan
Keyword(s):  
Ulcerative Colitis ◽  
Proinflammatory Cytokines ◽  
Activity Index ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Clinical Activity ◽  
Tnf Α ◽  
Significant Difference ◽  
And Control ◽  
Control Study

Abstract Background In this study, we investigated the importance of netrin-1 levels in ulcerative colitis (UC) in clinical activity of the disease, and its association with other proinflammatory cytokines IL-6 and TNF-α. Methods This study is a type of case–control study. Sixty-seven patients with UC (36 of them activation, 31 of remission) and 50 healthy controls were included in the study. UC patients; ‘Truelove Witts clinical activity index by remission (n = 31), mild activation (n = 21), moderate activation (n = 6) and severe activation (n = 9) were divided into groups. Netrin, IL-6 and TNF-α measurements in plasma samples were performed using enzyme-linked immunosorbent assay kit. Results Between the patient group and the control group; there was a statistically significant difference between netrin-1, IL-6, TNF-α, neutrophil, platelet (p &lt; 0.05 for all). The plasma netrin-1 mean of UC with severe activation group (139.21 ± 48.09 pg/ml) was statistically significantly higher than that of the mild activation (p = 0,037), remission group (p = 0,001) and control group(p = 0,011). The plasma netrin-1 mean of UC with moderate activation group was statistically significantly higher than that of the mild activation(p = 0,045) and remission group(p = 0,004). Conclusion Our results reveal that plasma netrin-1 levels have been shown to be associated with UC activation, similar to proinflammatory cytokines such as TNF-α and IL-6, in UC.

Therapeutic effect of anti-OX40L and anti-TNF-α MAbs in a murine model of chronic colitis

2003 ◽  
Vol 284 (4) ◽  
pp. G595-G603 ◽  
Author(s):  
T. Totsuka ◽  
T. Kanai ◽  
K. Uraushihara ◽  
R. Iiyama ◽  
M. Yamazaki ◽  
...  
Keyword(s):  
T Cells ◽  
Crohn’S Disease ◽  
T Cell ◽  
Crohn's Disease ◽  
Lamina Propria ◽  
Therapeutic Effect ◽  
Therapeutic Effects ◽  
Chronic Colitis ◽  
Tnf Α ◽  
Ifn Γ

Interaction of OX40 (CD134) on T cells with its ligand (OX40L) on antigen-presenting cells has been implicated in pathogenic T cell activation. This study was performed to explore the involvement of OX40/OX40L in the development of T cell-mediated chronic colitis. We evaluated both the preventive and therapeutic effects of neutralizing anti-OX40L MAb on the development of chronic colitis in SCID mice induced by adoptive transfer of CD4+CD45RBhighT cells as an animal model of Crohn's disease. We also assessed the combination of anti-OX40L and anti-TNF-α MAbs to improve the therapeutic effect. Administration of anti-OX40L MAb markedly ameliorated the clinical and histopathological disease in preventive and therapeutic protocols. In vivo treatment with anti-OX40L MAb decreased CD4+T cell infiltration in the colon and suppressed IFN-γ, IL-2, and TNF-α production by lamina propria CD4+T cells. The combination with anti-TNF-α MAb further improved the therapeutic effect by abolishing IFN-γ, IL-2, and TNF-α production by lamina propria CD4+T cells. Our present results suggested a pivotal role of OX40/OX40L in the pathogenesis of T cell-mediated chronic colitis. The OX40L blockade, especially in combination with the TNF-α blockade, may be a promising strategy for therapeutic intervention of Crohn's disease.

scholarly journals Transcribed ultraconserved region (T-UCR) uc.261 expression is closely correlated with disease activity and intestinal permeability in Crohn’s disease

2019 ◽  
Vol 12 ◽  
pp. 175628481988073
Author(s):  
Xiao-Xian Qian ◽  
Chen-Wen Cai ◽  
Han-Yang Li ◽  
Li-Jie Lai ◽  
Dong-Juan Song ◽  
...  
Keyword(s):  
Body Weight ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Intestinal Permeability ◽  
Activity Index ◽  
Trinitrobenzene Sulfonic Acid ◽  
T84 Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α

Objectives: Transcribed ultraconserved region (T-UCR) uc.261 is reported to participate in intestinal mucosa barrier damage in Crohn’s disease (CD). The aim of this study was to determine the association with disease activity and intestinal permeability. Methods: Uc.261 level in colon mucosa and Harvey-Bradshaw Index (HBI) were evaluated in 20 active CD patients. Uc.261 expression and transepithelial electrical resistance (TEER) were determined in Caco2 and T84 cells treated with tumor necrosis factor alpha (TNF-α), respectively. Body weight, disease activity index (DAI), colon length, histological index (HI), intestinal permeability to FITC-dextran, uc.261, and tight junction proteins (TJPs) levels were evaluated in BALB/C mice treated with saline enema, trinitrobenzene sulfonic acid (TNBS)/ethanol enema, and anti-TNF-α monoclonal antibody injection, respectively. Results: Uc.261 expression was overexpressed in CD patients, TNF-α treated cells, and colitis mice. Uc.261 expression was positively correlated with HBI ( r = 0.582, p = 0.007) in CD patients, and positively correlated with TNF-α concentration and negatively correlated TEER in Caco2 and T84 cells (all p < 0.05). Furthermore, uc.261 was positively correlated with DAI ( r = 0.824, p = 0.008), HI ( r = 0.672, p = 0.021), and intestinal permeability ( r = 0.636, p = 0.012), while negatively correlated with body weight ( r = –0.574, p = 0.035), colon length ( r = –0.866, p = 0.017), and TJP expression (all p < 0.05) in colitis mice. Conclusions: Uc.261 expression was closely correlated with disease activity and intestinal permeability in CD. Anti-TNF-α treatment may play its role through suppressing uc.261 expression in colitis mice.

scholarly journals Serum Syndecan-1 Levels and Its Relationship to Disease Activity in Patients with Crohn’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Cem Çekiç ◽  
Adnan Kırcı ◽  
Sezgin Vatansever ◽  
Fatih Aslan ◽  
Huriye Erbak Yılmaz ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Activity Index ◽  
Normal Population ◽  
Disease Activity Index ◽  
Serum Levels ◽  
Control Group ◽  
Serum Samples ◽  
Reactive Protein

Background. Syndecan-1 (SDC-1), a member of the family of heparan sulfate proteoglycans, plays an important role in the resolution of inflammation. This study aimed to investigate the relationship between SDC-1 and disease activity in Crohn’s disease (CD).Methods. Serum samples of 54 patients with CD and 30 healthy controls were obtained. First, SDC-1 levels of the CD patients were compared to the control group. Subsequently, SDC-1 levels were analyzed in patients with CD in active and remission periods. Finally, SDC-1 efficacy in predicting disease activity was evaluated by performing correlation analysis between SDC-1 and C-reactive protein (CRP) and Crohn’s disease activity index (CDAI).Results. SDC-1 level was higher in the CD group (61.9 ± 42.6 ng/mL) compared with the control group (34.1 ± 8.0 ng/mL)p=0.03. SDC-1 levels were higher in active CD patients (97.1 ± 40.3 ng/mL) compared with those in remission (33.7 ± 13.5 ng/mL)p<0.001. A significant positive correlation was found between SDC-1 and CRP (r=0.687,p<0.001) and between SDC-1 and CDAI (r=0.747,p<0.001).Conclusion. Serum levels of SDC-1 are higher in CD compared to the normal population and can be an effective marker of disease severity.

scholarly journals Mesenchymal stromal cells of bone marrow and azathioprine in Crohn's disease therapy

2018 ◽  
Vol 90 (2) ◽  
pp. 47-52 ◽  
Author(s):  
O V Knyazev ◽  
A V Kagramanova ◽  
N A Fadeeva ◽  
A A Lishchinskaya ◽  
O N Boldyreva ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Inflammatory Cytokines ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Transforming Growth Factor ◽  
Activity Index ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Crohn's disease (CD) is a chronic, recurring disease of the gastrointestinal tract of unclear etiology. One of the new approaches to CD therapy is the use of the possibilities of stem cells, in particular, mesenchymal stromal cells (MSCs). Currently, the use of MSC in clinical practice for the treatment of chronic inflammatory and autoimmune diseases is being studied in patients who receive concomitant therapy with other immunomodulatory medications. Aim. To evaluate the effectiveness of MSCs therapy in patients with CD receiving azathioprine (AZA). Materials and methods. The study included 34 patients with inflammatory (luminal) form of CD. The 1st group of patients (n=15) received anti-inflammatory therapy using MSCs culture in combination with AZA. The 2nd group (n=19) received MSCs without AZA. The severity of the attack was assessed in points in accordance with the of Crohn's disease activity index (CDAI). Immunoglobulins (IgA, IgG, IgM), interleukins (IL) 1β, 4, 10, tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), transforming growth factor-1β (TGF-1β), C-reactive protein (CRP), platelets and erythrocyte sedimentation rate (ESR) at 2, 6 and 12 months from the beginning of MSCs therapy. Results. The initial mean CDAI in the 1st group was 337.6±17.1 points, in the 2nd group - 332.7±11.0 points (p=0.3). In both groups of patients there was a significant decrease in CDAI after 2 months. From the beginning of therapy MSCs: in the 1st group to 118.9±12.4 points, in the 2nd - 120.3±14.1 points (p=0.7), after 6 months - 110.3±11.1 and 114.3±11.8 points (p=0.8), respectively. After 12 months CDAI in the 1st group was 99.9±10.8 points, in the 2nd group it was 100.6±12.1 points (p=0.8). The level of IgA, IgG, IgM was significantly lower in the group of patients with a longer history of the disease and long-term ASA. After the introduction of MSC in both groups of patients with BC, there was a tendency for the growth of pro - and anti-inflammatory cytokines, with a significantly lower level of pro-inflammatory cytokines - INF-γ, TNF-α, IL-1β - in the 1st group, indicating potentiation of the immunosuppressive effect of MSCs and AZA, which provides a more pronounced anti-inflammatory effect. Conclusion. Transplantation of MSCs promotes an increase in the serum of patients with CD initially reduced concentration of IG, cytokines and restoring their balance as the onset of clinical remission. The combination with AZA has a more pronounced anti-inflammatory effect.

scholarly journals Significance of ultrasonography of the terminal ileum in moderate Crohn's disease

2006 ◽  
Vol 63 (9) ◽  
pp. 787-792 ◽  
Author(s):  
Leposava Lukic-Kostic ◽  
Jasna Jovic ◽  
Slobodan Sekulovic
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Lymph Nodes ◽  
Terminal Ileum ◽  
Clinical Laboratory ◽  
Activity Index ◽  
Disease Activity Index ◽  
Unknown Etiology ◽  
Control Group ◽  
Ultrasonographic Examination

Background/aim: Crohn's disease (CD) is a chronic granulomatous inflammatory disease of unknown etiology, involving any part of the gastrointestinal tract, and frequently followed by extra intestinal manifestations. The use of ultrasonography plays a significant role in diagnosing this disease, as well as in monitoring the effects of the therapy. The aim of this study was to assess the use of ultrasonographic diagnostics in the patients with moderate serious and the mild form of CD. Methods. The study involved 30 patients both sexes with CD of moderate form determined using the standard diagnostics, according to the Crohn's Disease Activity Index - CDAI ranging from 220?400. The patients were divided into two groups with CDAI > 320 (Ia), and CDAI between 220 and 320 (Ib), respectively. The Control group was made of 19 patients with the mildly active stage of the disease and the CDAI values in the range from 100?220. The patients were submitted to an ultrasonographic examination of the terminal ileum affected with CD in order to determine the length of the affected segment of intestine, the thickness of the wall, the changes of the structure of the wall, the changes of the surrounding mesenterium with the enlarged lymph nodes. CD complications, abscesses, and enteroenteral fistulas were investigated, too. Results. The comparison of the ultrasonographic findings of the three groups revealed that more serious clinical laboratory image of CD significantly correlated with the higher length of the affected segment (p < 0.001), higher thickness of the wall (p < 0.001), the higher number and the larger lymph nodes of the mesenterium (p < 0.001). Only the most serious patients were found to have abscess of the ileocecal area (Ia ? 40%). There was no difference found between the groups regarding the occurrence of enteroenteral fistulas. Conclusion. Considering the obtained results and data from the literature, it could be concluded that an ultrasonographic examination of the ileocecal area plays an important role in the diagnostic procedure in the management of a patient with CD. Of particular significance is the possibility to use this examination in monitoring the effects of the therapy in patients with CD.

scholarly journals The role of enteroclysis and roentgen anatomy of jejunum and ileumin Crohn's disease

2005 ◽  
Vol 58 (9-10) ◽  
pp. 437-443
Author(s):  
Dragan Krivokuca ◽  
Djordjije Saranovic ◽  
Milivoje Vukovic ◽  
Laslo Puskas ◽  
Gordana Stankovic ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gastrointestinal Symptom ◽  
Morphological Changes ◽  
Healthy People ◽  
Control Group ◽  
Study Group ◽  
Double Contrast ◽  
Mucosal Folds

Introduction The aims of this research were: I) to establish the value ofen-teroclysis in detection of morphological changes of jejunum and ileum in cases with suspected Crohn's disease and 2) to establish types of morphological changes of jejunum and ileum in patients with Crohn's disease. Material and methods The study compared two groups of people who voluntarily accepted to be examined: a control group and a study group. The control group included 11 healthy people, without gastrointestinal symptom. The study group included 16 patients with Crohn's disease. Single and double-contrast enteroclysis were performed in both groups. Afterwards, we defined parameters which were compared in these groups. Conclusions We concluded that according to statistics there are significantly lower values of the width of the jejunal and Heal lumen and the number of mucosa/folds (per I cm) of the jejunal and Heal wall in the examined group in contrast to the control group. Also, according to statistics there are significantly higher values of the width of the jejunal and ileal wall and the thickness of mucosal folds of the jejunum and ileum in the study group in contrast to the control group.

scholarly journals Correlation of Paraoxonase-1 with the Severity of Crohn’s Disease

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2603
Author(s):  
Katarzyna Szczeklik ◽  
Tomasz Mach ◽  
Dorota Cibor ◽  
Danuta Owczarek ◽  
Jacek Sapa ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Sensitivity And Specificity ◽  
Activity Index ◽  
Area Under The Curve ◽  
Density Lipoprotein ◽  
High Sensitivity ◽  
Paraoxonase 1 ◽  
Control Group ◽  
Operating Characteristics

Diagnostics of Crohn’s disease (CD) requires noninvasive biomarkers facilitating early detection and differentiation of the disease. Therefore, in this study, we aimed to determine the relationship between paraoxonase-1 (PON-1), the severity of CD, oxidative stress, and inflammation in CD. The CD activity index was based on the current classification. Plasma PON-1 was measured in 47 patients with CD, and in 23 control volunteers. Using quantitative variables such as receiver operating characteristics (ROC) (area under the curve (AUC)), the diagnostic utility of PON-1 in differentiating the severity of CD was assessed. Circulating PON-1 was found to be decreased in the CD group compared to the control group (269.89 vs. 402.56 U/L, respectively), and it correlated well with the disease activity. PON-1 correlated positively with hemoglobin (Hb) (r = 0.539, p < 0.001), hematocrit (Ht) (r = 0.48, p < 0.001), total cholesterol (TC) (r = 0.343, p < 0.001), high density lipoprotein (HDL) (r = 0.536, p < 0.001), low density lipoprotein (LDL) (r = 0.54, p < 0.001), and triglyceride (TG) (r = 0.561, p < 0.001) and correlated negatively with white blood cell count (WBC) (r = −0.262, p = 0.029), platelet count (PLT) (r = −0.326, p = 0.006), C-reactive protein (CRP) (r = −0.61, p < 0.001), and malondialdehyde (MDA) (r = −0.924, p < 0.001). PON-1 as a marker for CD differentiation possessed a sensitivity and specificity of 93.62% and 91.30%, respectively. CD was found to be associated with the decrease in the levels of PON-1, which correlates well with activity of the disease and reflects the intensification of inflammation, as well as intensified lipid peroxidation. High sensitivity and specificity of PON-1 determines its selection as a good screening test for CD severity.

scholarly journals Biology of Inflammation in Crohn's Disease: Mechanisms of Action of Anti-TNF-αAlpha Therapy

2000 ◽  
Vol 14 (suppl c) ◽  
pp. 13C-16C ◽  
Author(s):  
Stephan R Targan
Keyword(s):  
Monoclonal Antibody ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
The Body ◽  
Primary Role ◽  
T Helper 1 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
In Vitro Investigation

Several recent trials of intravenously administered antitumour necrosis factor-alpha (TNF-α) monoclonal antibody have shown dramatic responses among patients with Crohn’s disease. These results indicate a primary role for TNF-αin the mediation of altered mucosal immune function in this disease. Clinical responses in patients treated with a single infusion of anti-TNF-αpersisted for as long as one year. The prolonged period of clinical benefit shows that the effect of short term TNF-αelimination remains long after the monoclonal antibody has cleared the body. Corresponding in vitro investigation has shown that T helper 1 (Th1) -mediated cytokine production of interferon-gamma is downregulated in the involved mucosa to a level consistent with that seen in uninflamed mucosa. These results suggest that TNF-α-specific augmentation of mucosal Th1 function is the process that is altered by removal of TNF-αand that produces such persistent responses. Understanding how TNF-αmodulates mucosal Th1 function may lead to the definition of a key feature of Crohn’s disease pathogenesis.

Mucosal Expression of Basic Fibroblastic Growth Factor, Syndecan 1 and Tumour Necrosis Factor-α in Crohn’s Disease in Deep Remission under Treatment with Anti-TNFα Antibodies

2014 ◽  
Vol 23 (3) ◽  
pp. 261-265 ◽  
Author(s):  
Antonio Tursi ◽  
Walter Elisei ◽  
Mariabeatrice Principi ◽  
Cosimo Damiano Inchingolo ◽  
Rosanna Nenna ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Growth Factor ◽  
Crohn's Disease ◽  
Control Group ◽  
Rt Pcr ◽  
Molecular Pattern ◽  
Tnf Α ◽  
Factor Α ◽  
Basic Fibroblastic Growth Factor ◽  
Necrosis Factor

Background & Aims: Both inflammation and fibrosis may be detected in Crohn's disease (CD). The molecular pattern of Basic Fibroblastic Growth Factor (bFGF) and Syndecan-1 (SD1) expression is altered in stenosing CD, but we do not know what the behaviour of this teamwork factor is in CD in deep remission under treatment with anti-TNFα antibodies. Our aim was to compare the expression of bFGF, SD1 and TNF-α in patients with CD in deep remission under treatment with Infliximab (IFX) or Adalimumab (ADA) and a control group of patients with active CD.Methods: We assessed the expression of bFGF, SD1 and TNF-α in 10 patients with active CD and in 28 patients with CD in sustained deep remission for at least 6 months. All patients underwent surveillance colonoscopy with biopsies, while receiving maintenance therapy with IFX or ADA. Analysis was conducted by real-time reverse transcriptase PCR (RT-PCR) in biopsy samples.Results: We found that bFGF, SD1 and TNF-α were significantly reduced under treatment with anti-TNFα versus controls (p=0.000). bFGF and SD1 expression were similar between IFX and ADA patients (p=0.335 and p=0.289, respectively), while TNF-α was significantly under-expressed in ADA patients (p=0.008).Conclusions: bFGF, SD1 and TNF-α are significantly reduced in CD patients in deep remission under treatment with anti-TNFα, likely as an expression of optimal control of inflammation. The significance of the TNF-α under-expression in patients under treatment with ADA with respect to those under treatment with IFX should be elucidated in further studies.

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