1. |
- Ahluwalia, Bani, et al.
(author)
-
Effects of Aloe barbadensis Mill. extract (AVH200 (R)) on human blood T cell activity in vitro
- 2016
-
In: Journal of Ethnopharmacology. - : Elsevier BV. - 0378-8741 .- 1872-7573. ; 179, s. 301-309
-
Journal article (peer-reviewed)abstract
- Ethnopharmacological relevance: Aloe barbadensis Mill. (Aloe vera) is a widely used medicinal plant well reputed for its diverse therapeutic applications. It has been used for thousands of years in folk medicine to treat various conditions and the Aloe vera gel has been reported to possess anti-inflammatory as well as immunostimulatory and immunomodulatory properties. However, the mode of action is still unclear. Aim of the study: The aim of this study was determine the effects of two well-defined A. barbadensis Mill. extracts AVH200 (R) and AVE200 on human blood T cells in vitro. Materials and methods: Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated polyclonally in the presence or absence of AVH200 (R) and AVE200. The T cell phenotype was investigated by flow cytometry, cell proliferation was determined by CFSE dye and thymidine assay, respectively and cytokine secretion was determined by MSD (R) Multi-Spot Assay system and ELISA. Results: The presence of AVH200 (R) resulted in a reduced expression of CD25 among CD3(+) T cells and suppression of T cell proliferation in a dose dependent manner. Furthermore, AVH200 (R) reduced the expression of CD28 on CD3(+) T cells. AVH200 (R) also reduced the secretion of IL-2, IFN-gamma and IL-17A in PBMC cultures. The AVH200 (R) dose dependent reduction in T cell activation and proliferation recorded in the cell cultures was not due to apoptosis or cell death. Additionally, AVH200 (R) was found to be more effective as compared to AVE200 in reducing T cell activation and proliferation. Conclusion: AVH200 (R) has the potential to reduce the activation, proliferation and cytokine secretion of healthy human blood T cells. Our study suggests that AVH200 (R) has a suppressive effect on human blood T cells in vitro.
|
|
2. |
- Bennet, Sean, et al.
(author)
-
Global Cytokine Profiles and Association With Clinical Characteristics in Patients With Irritable Bowel Syndrome
- 2016
-
In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 111:8, s. 1165-1176
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: Evidence suggests that patients with irritable bowel syndrome (IBS) have an altered cytokine profile, although it is unclear whether cytokines are linked with symptom severity. We aimed to determine whether global serum and mucosal cytokine profiles differ between IBS patients and healthy subjects and whether cytokines are associated with IBS symptoms. METHODS: Serum from 144 IBS patients and 42 healthy subjects was analyzed for cytokine levels of interleukin (IL)-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, interferon (IFN)-gamma and tumor necrosis factor (TNF) by MSD MULTI-ARRAY. In total, 109 IBS and 36 healthy sigmoid colon biopsies were analyzed for mRNA expression of IL-8, IL-10, TNF, and FOXP3 by quantitative reverse transcription PCR. Multivariate discrimination analysis evaluated global cytokine profiles. Rectal sensitivity, oroanal transit time, and psychological and gastrointestinal symptom severity were also assessed. RESULTS: Global cytokine profiles of IBS patients and healthy subjects overlapped, but cytokine levels varied more in IBS patients. Serum levels of IL-6 and IL-8 tended to be increased and levels of IFN-gamma tended to be decreased in IBS patients. Mucosal mRNA expression of IL-10 and FOXP3 tended to be decreased in IBS patients. Within both the full study cohort and IBS patients alone, serum level of TNF was associated with looser stool pattern, while subjects with more widespread somatic symptoms had increased serum levels of IL-6. Although neither IBS bowel habit subgroups nor patients with possible post-infectious IBS were associated with distinct cytokine profiles, a small cluster of IBS patients with comparatively elevated immune markers was identified. CONCLUSIONS: Global cytokine profiles did not discriminate IBS patients from healthy subjects, but cytokine profiles were more varied among IBS patients than among healthy subjects, and a small subgroup of patients with enhanced immune activity was identified. Also, association of inflammatory cytokines with some clinical symptoms suggests that immune activation may be of importance in a subset of IBS patients.
|
|
3. |
|
|
4. |
|
|
5. |
- Magnusson, Maria K, 1972, et al.
(author)
-
Cultured blood T-cell responses predict anti-TNF therapy response in patients with ulcerative colitis
- 2015
-
In: Alimentary Pharmacology & Therapeutics. - : Wiley. - 0269-2813. ; 41:11, s. 1149-1161
-
Journal article (peer-reviewed)abstract
- BackgroundAnti-tumour necrosis factor (TNF) therapy is used for treatment of ulcerative colitis (UC). As approximately 30% of patients with UC do not benefit from the treatment, it is of clinical interest to identify biomarkers of response before therapy is initiated. AimTo identify prognostic biomarkers of anti-TNF therapy response in anti-TNF therapy-naive patients with UC. MethodsPeripheral blood cells were obtained from 56 patients with UC before therapy started. Thirty-four patients were included in an exploratory cohort and 22 patients in a validation cohort. Blood cells were stimulated in vitro with influenza vaccine with and without anti-TNF. T-cell surface receptor expression and cytokine release were determined (in total 17 variables). Treatment response was evaluated using the Mayo score 12-14weeks after the first infusion. ResultsIn the exploratory cohort, blood cells from the patients showed stronger anti-TNF-dependent suppression of T-cell surface receptor expression and cytokine secretion among therapy responders than nonresponders. In particular, anti-TNF suppressed the expression of CD25 on T cells and secretion of interleukin 5, to a higher degree in responders than in nonresponders. These variables were used to a create model to predict therapy outcome, which was confirmed in the validation cohort. Correct classification of future therapy response was achieved in 91% of the cases in the validation cohort. ConclusionThe effects of anti-TNF on cultured blood T cells, obtained before therapy started, predict treatment outcome in patients with UC.
|
|
6. |
|
|
7. |
- Magnusson, Maria K, 1972, et al.
(author)
-
The Mucosal Antibacterial Response Profile and Fecal Microbiota Composition Are Linked to the Disease Course in Patients with Newly Diagnosed Ulcerative Colitis
- 2017
-
In: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998. ; 23:6, s. 956-966
-
Journal article (peer-reviewed)abstract
- Background: The clinical disease course of ulcerative colitis (UC) varies substantially between individuals and can currently not be reliably predicted. The gut microbiota and the host's immune defense are key players for gut homeostasis and may be linked to disease outcome. The aim of this study was to determine fecal microbiota composition and mucosal antibacterial response profile in untreated patients with newly diagnosed UC and the impact of these factors on disease course. Methods: Stool samples and intestinal biopsies were obtained from therapy-naive newly diagnosed patients with UC. Patients were defined to have mild or moderate/severe disease course assessed by disease activity during the 3 years follow-up. Fecal microbiota was analyzed by the GA-map Dysbiosis test (n = 18), and gene expression in intestinal biopsies was analyzed by RT2 Profiler polymerase chain reaction array (n = 13) and real-time polymerase chain reaction (n = 44). Results: At the time of diagnosis of UC, the fecal microbiota composition discriminated between patients with mild versus moderate/severe disease course. Also, the mucosal antibacterial gene expression response profile differed between patients with mild versus moderate/severe disease course with bactericidal/permeability-increasing protein (BPI) being most important for the discrimination. Mucosal bactericidal/permeability-increasing protein gene expression at diagnosis was higher in patients with mild versus moderate/severe disease course when confirmed in a larger patient cohort (P = 0.0004, n = 44) and was a good predictor for the number of flares during the 3 years follow-up (R-2 = 0.395, P < 0.0001). Conclusions: In patients with newly diagnosed UC, fecal microbiota composition and mucosal antibacterial response profile, especially bactericidal/permeability-increasing protein, are linked to disease course.
|
|
8. |
- Mavroudis, Georgios, et al.
(author)
-
Mucosal and Systemic Immune Profiles Differ During Early and Late Phases of the Disease in Patients With Active Ulcerative Colitis
- 2019
-
In: Journal of Crohns & Colitis. - : Oxford University Press (OUP). - 1873-9946. ; 13:11, s. 1450-1458
-
Journal article (peer-reviewed)abstract
- Background and Aims: Alterations in the immunopathogenesis in ulcerative colitis [UC] during the disease course have been proposed. We therefore aimed to determine mucosal and systemic immune profiles in individual patients at the time of diagnosis [early disease] and after 10 years [late disease]. Methods: Patients with UC provided serum and mucosal biopsies during a flare in early and in late disease. Serum samples were analysed using the Olink Proseek Inflammation panel. mRNA gene expression of biopsies was analysed using the Qiagen RT2 Profiler PCR Arrays Antibacterial response and T Helper Cell Differentiation. Results: Orthogonal projections to latent structures discriminant analyses [OPLS-DA] demonstrated that the profile of 15 serum proteins discriminated in early and late disease [R2 = 0.84, Q2 = 0.65] in 15 UC patients. Eight of these proteins were differently expressed between the groups [Q <0.05]. Further, OPLS-DA of the mRNA profiles in biopsies strongly discriminated early and late disease with high predictability [R2 = 0.96, Q2 = 0.89]; 42 genes were differently expressed at the two time points [Q <0.05]. Finally, principal component analysis showed that T helper [Th] 1- and Th2-related genes were associated with early disease and late disease, respectively, and hierarchical cluster analysis was able to cluster patients with early from late disease with only minor overlap. Conclusions: Mucosal and systemic immune profiles differ between early and late disease in patients with active UC, with a transition from a Th1- to a Th2-driven disease in the intestine. Improved understanding of the variation in immunopathogenesis during the disease course in UC is important to guide individualised treatment decision making.
|
|