Butanol Purified Food Allergy Herbal Formula-2 Has an Immunomodulating Effect ex-vivo in Pediatric Crohn's Disease Subjects

Background: TNF-α has a major role in the pathogenesis of Crohn's disease (CD). In contrast, GM-CSF may be beneficial for its anti-inflammatory role in a subset of patients with CD with antibodies against GM-CSF as seen in prior trials of GM-CSF which resulted in clinical improvement in CD. We developed butanol purified Food Allergy Herbal Formula-2 (B-FAHF-2) by refining FAHF-2. FAHF-2 suppressed TNF-α production by human peripheral blood mononuclear cells (PBMCs) and colonic mucosa, and abrogated colitis in a murine model. We sought to examine the effect of B-FAHF-2 and the herbs that comprise it on TNF-α and GM-CSF production as a potential herbal therapy for the treatment of CD.Methods: B-FAHF-2 was examined using high pressure liquid chromatography (HPLC) and compared to the original formulation, FAHF-2. PBMCs from pediatric patients with CD were cultured with lipopolysaccharide and B-FAHF-2, individual herbs or medium alone. Colonic biopsy specimens were cultured with or without B-FAHF-2. TNF-α and GM-CSF were measured by enzyme-linked immunosorbent assay (ELISA). B-FAHF-2 efficacy was tested in vivo in the CD45Rbhi transfer model.Results: B-FAHF-2 had a similar HPLC fingerprint as FAHF-2 but decreased TNF-α production by PBMCs and colonic mucosa from pediatric CD subjects at 20% of the FAHF-2 dose. B-FAHF-2 increased GM-CSF production by PBMCs and colonic mucosa from pediatric CD subjects including those with antibodies to GM-CSF. Of B-FAHF-2's herbal constituents, only Huang Bai suppressed TNF-α and increased GM-CSF production. In the murine model, B-FAHF-2 treatment alleviated colitis.Conclusions: B-FAHF-2 decreased TNF-α production by PBMCs and colonic mucosa from pediatric subjects at a lower dose than FAHF-2. B-FAHF-2 also increased GM-CSF production by PBMCs independent of antibodies. B-FAHF-2 may have a benefit in CD patients.

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The influence of vitamin D on M1 and M2 macrophages in patients with Crohn's disease

Innate Immunity ◽

10.1177/1753425917721965 ◽

2017 ◽

Vol 23 (6) ◽

pp. 557-565 ◽

Cited By ~ 19

Author(s):

Serge Dionne ◽

Carl-Frederic Duchatelier ◽

Ernest G Seidman

Keyword(s):

Vitamin D ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Vitamin D Supplementation ◽

Bacterial Clearance ◽

Gm Csf ◽

Tnf Α ◽

Anti Inflammatory ◽

M2 Phenotype ◽

M1 And M2 Macrophages

Defective bacterial clearance by macrophages plays an important role in Crohn’s disease (CD). Phenotypes and functions of inflammatory M1 and anti-inflammatory M2 have not been studied in CD. Vitamin D supplementation reduces the severity of CD by unclear mechanisms. We studied macrophage characteristics in CD and controls and the effects of 1,25 vitamin D (1,25D). PBMC were isolated from CD patients and controls. M1 and M2 were generated by culturing of monocytes with GM-CSF and M-CSF, respectively. CD M1 and M2 showed normal phagocytosis and chemotaxis to CCL2 and fMLP. LPS-induced production of TNF-α, IL-12p40 and IL-10 was comparable between groups. Phagocytosis was unaltered with 1,25D; migration only increased marginally. M1 produced more IL-12p40 and TNF-α; IL-10 was greater in M2. 1,25D markedly decreased IL-12p40 by M1 and M2. 1,25D decreased TNF-α in CD M1; IL-10 levels were unaffected. M2 express F13A1, PTGS2, CD163, CXCL10, CD14 and MMP2, whereas TGF-β, CCL1 and CYP27B1 expression was higher in M1. Marker expression was similar between CD and controls. M1 and M2 markers were not differentially modulated by 1,25D. CD macrophages are not functionally or phenotypically different vs. controls. 1,25D markedly decreased pro-inflammatory M1 cytokines but did not modulate polarization to anti-inflammatory M2 phenotype.

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Crohn’s Disease Patients with Depression Exhibit Alterations in Monocyte/Macrophage Phenotype and Increased Proinflammatory Cytokine Production

Digestive Diseases ◽

10.1159/000501122 ◽

2019 ◽

Vol 38 (3) ◽

pp. 211-221 ◽

Cited By ~ 4

Author(s):

Yu Tang ◽

Li Zhao ◽

Na Lei ◽

Pingrun Chen ◽

Yan Zhang

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Plasma Levels ◽

Proinflammatory Cytokine ◽

Transforming Growth Factor ◽

Macrophage Polarization ◽

Depression Scale ◽

Enzyme Linked Immunosorbent Assay ◽

M1 Macrophage ◽

Tnf Α

Background: Crohn’s disease (CD) is strongly associated with depression, but the mechanisms underlying this relationship are not fully understood. Recently, neuroimmunological studies have demonstrated that proinflammatory monocytes/macrophages play a key role in the pathogenesis of depression. The present study investigates monocyte/macrophage phenotypes and plasma cytokine levels in CD. Methods: Eligible CD patients were divided into nondepressed and depressed groups according to Hospital Anxiety and Depression Scale for depression (HADS-D). The Harvey-Bradshaw index (HBI), the Simple Endoscopic Score for Crohn’s disease (SES-CD), and the Global Histological Disease Activity Score (GHAS) were compared between the 2 groups. Immunohistochemistry was performed to quantify the expression of CD68, inducible nitic oxide synthase (iNOS), and CD163 in colon mucosa. Enzyme-linked Immunosorbent Assay was used to detect plasma levels of M1 macrophage-secreted cytokines (tumor necrosis factor [TNF]-α, interleukin 6 [IL-6], IL-1β) and M2 cytokines (transforming growth factor [TGF]-β1, IL-10, C-C motif chemokine ligand 22, [CCL22]). Flow cytometry was utilized to determine peripheral blood monocyte subsets. Results: Depressed CD patients (n = 91) presented higher HBI, SES-CD, GHAS than the nondepressed patients (n = 42). Intermediate (CD14++CD16+) and nonclassical monocytes (CD14+CD16++) percentages, integrated optical density (IOD) of iNOS+ cells representing M1 macrophages, and plasma levels of TNF-α, IL-6, IL-1β were increased while classical monocyte (CD14++CD16–) percentage, IOD of CD163+ cells representing M2 macrophages, and IL-10 plasma levels were decreased in depressed versus nondepressed CD patients. Plasma levels of TNF-α, IL-6, IL-1β correlated with HADS-D scores. Conclusion: Monocytes subpopulation disequilibrium toward intermediate and nonclassic phenotypes and macrophage polarization toward M1 phenotype with increased proinflammatory cytokine release are more likely to be found in CD patients with depressive symptoms.

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Imbalance of the interleukin 1 system in colonic mucosa—association with intestinal inflammation and interleukin 1 receptor agonist genotype 2

Gut ◽

10.1136/gut.41.5.651 ◽

1997 ◽

Vol 41 (5) ◽

pp. 651-657 ◽

Cited By ~ 117

Author(s):

T Andus ◽

R Daig ◽

D Vogl ◽

E Aschenbrenner ◽

G Lock ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Colonic Mucosa ◽

Intestinal Inflammation ◽

Interleukin 1 ◽

Mucosal Inflammation ◽

Enzyme Linked Immunosorbent Assay ◽

Biopsy Specimens ◽

Genotype 2 ◽

Normal Controls

Background—Interleukin 1 (IL-1) α and β are potent cytokines which play key roles in inflammation. They are controlled by IL-1 receptor antagonist (IL-1ra).Aims—To investigate the influence of mucosal inflammation and IL-1ra genotype on the IL-1ra:IL-1 balance.Patients and methods—IL-1α, IL-1β, and IL-1ra were measured by enzyme linked immunosorbent assay (ELISA) in biopsy specimens taken from inflamed and non-inflamed colon of 60 patients with Crohn’s disease (CD), 34 with ulcerative colitis (UC), 15 inflammatory controls, and 103 non-inflamed controls. IL-1ra genotype was determined by polymerase chain reaction and gel electrophoresis.Results—IL-1α and IL-1β were significantly increased in inflamed mucosa in inflammatory bowel disease (IBD) (CD: 53.5 (22.4) and 409.9 (118.7) pg/mg protein, respectively; UC: 18.9 (6.8) and 214.5 (78.2) pg/mg, respectively) and non-IBD patients (19.2 (7.4) and 281.4 (121.0) pg/mg, respectively; p<0.0001) compared with normal controls (2.8 (0.6) and 30.6 (5.6) pg/mg, respectively). In CD IL-1α and β were also significantly increased in non-inflamed mucosa (6.1 (1.3) pg/mg and 88.7 (17.4) pg/mg, respectively; p<0.0012). IL-1ra:(IL-1α+β) ratios were significantly decreased in inflamed mucosa of patients with CD (182 (45); p<0.0001), UC (425 (136); p=0.0018) and without IBD (221 (76); p<0.0001), and in non-inflamed mucosa in CD (369 (149); p<0.0001) compared with normal controls (1307 (245); p<0.0001). Patients with IL-1ra genotype 2 had slightly but significantly reduced mucosal IL-1ra concentrations (p=0.003). The greatest difference was seen in colonic biopsy specimens from patients with inflamed Crohn’s disease.Conclusion—Mucosal inflammation can modulate the balance of the IL-1:IL-1ra system in colonic mucosa.

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Emergence of perianal fistulae and ulceration in a murine model of IBD: A novel model of perianal Crohn's disease (CD)

Gastroenterology ◽

10.1016/s0016-5085(01)80601-6 ◽

2001 ◽

Vol 120 (5) ◽

pp. A122-A122

Author(s):

S COHN ◽

A VIDRICH ◽

M SUMMY ◽

C MOSKALUK ◽

F COMINELLI

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Murine Model ◽

Perianal Crohn’S Disease ◽

Perianal Fistulae ◽

Novel Model ◽

Perianal Crohn's Disease

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Predictive factors of response to anti-TNF α treatment of complex ano-perineal fistulas in Crohn’s disease.

10.26226/morressier.59a6b34cd462b80290b55a24 ◽

2017 ◽

Author(s):

maroua hafi

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Predictive Factors ◽

Tnf Α

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THE EVALUATION OF SERUM SEROTONIN LEVEL AMONG PATIENTS WITH CROHN’S DISEASE AND ITS IMPACT ON QUALITY OF LIFE

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa347.131 ◽

2021 ◽

Vol 27 (Supplement_1) ◽

pp. S55-S55

Author(s):

Marcin Sochal ◽

Piotr Bialasiewicz ◽

Agata Gabryelska ◽

Renata Talar-Wojnarowska ◽

Jakub Fichna ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Sleep Quality ◽

Sleep Fragmentation ◽

Clinical Severity ◽

Serotonin Level ◽

Intestinal Physiology ◽

Tnf Α

Abstract Background and aims Serotonin affects intestinal physiology, mood, as well as circadian rhythm. Moreover, serotonin has proinflammatory function. Therefore, the aim of this study was to investigate the role of serotonin in clinical severity of Crohn’s Disease (CD) and its effect on pain and sleep quality. Methods Fifty-nine CD patients (34 in exacerbation and 25 in remission according to the Harvey-Bradshaw Index-HBI) and 25 health control individuals(HC) were recruited. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and subjective severity of pain by the Visual Analog Scale (VAS). Seventeen patients were treated with anti-TNF-α induction therapy for 14 weeks. Results Serotonin level was higher in CD (145.12ng/mL, IQR:98.14–179.25) compared to HC (87.52ng/mL, IQR:70.04–129.39; p=0.002) and in exacerbation of CD (157.66ng/mL, IQR:111.94–197.64) compared to remission (122.33ng/mL, IQR:83.28–163.67; p=0.029). Serotonin level with cut-off point of 92.45 ng/mL is useful for distinguishing participants with CD from HC (sensitivity: 78%, specificity: 60%, positive predictive value: 82%). Positive correlation between serotonin and HBI (r=0.279, p=0.032) and severity of diarrhoea (r=0.260, p=0.047) were found. Serotonin does not correlate with PSQI (r=0.152, p=0.168), but correlates with presence of sleep fragmentation for example by getting up to use the bathroom (joined 5b-5j PSQI questions; r=0.270, p=0.039). Correlations between serotonin and VAS were also obtained (r=0.220, p=0.045). Moreover, serotonin level significantly decreased after anti-TNF-α therapy (192.35ng/mL, IQR:150.36–225.56 vs. 121.11ng/mL, IQR:91.28–188.87; p=0.006). The study was funded by National Science Centre, Poland (#2018/31/N/NZ5/03715). Conclusions Serotonin level correlates with the severity of CD and decreases after anti-TNF-α therapy. It is associated with sleep fragmentation, which may be caused by diarrhea.

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Glycyrrhizin Attenuates Carcinogenesis by Inhibiting the Inflammatory Response in a Murine Model of Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22052609 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2609

Author(s):

Guifeng Wang ◽

Keiichi Hiramoto ◽

Ning Ma ◽

Nobuji Yoshikawa ◽

Shiho Ohnishi ◽

...

Keyword(s):

Colorectal Cancer ◽

Dna Damage ◽

Stem Cell ◽

Inflammatory Response ◽

Murine Model ◽

Licorice Root ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Stem Cell Markers ◽

Tnf Α

Glycyrrhizin (GL), an important active ingredient of licorice root, which weakens the proinflammatory effects of high-mobility group box 1 (HMGB1) by blocking HMGB1 signaling. In this study, we investigated whether GL could suppress inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer. ICR mice were divided into four groups (n = 5, each)—control group, GL group, colon cancer (CC) group, and GL-treated CC (CC + GL) group, and sacrificed after 20 weeks. Plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using an enzyme-linked immunosorbent assay. The colonic tissue samples were immunohistochemically stained with DNA damage markers (8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxy-guanosine), inflammatory markers (COX-2 and HMGB1), and stem cell markers (YAP1 and SOX9). The average number of colonic tumors and the levels of IL-6 and TNF-α in the CC + GL group were significantly lower than those in the CC group. The levels of all inflammatory and cancer markers were significantly reduced in the CC + GL group. These results suggest that GL inhibits the inflammatory response by binding HMGB1, thereby inhibiting DNA damage and cancer stem cell proliferation and dedifferentiation. In conclusion, GL significantly attenuates the pathogenesis of AOM/DSS-induced colorectal cancer by inhibiting HMGB1-TLR4-NF-κB signaling.

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