scholarly journals Lactobacilli Supplemented with Larch Arabinogalactan and Colostrum Stimulates an Immune Response towards Peripheral NK Activation and Gut Tolerance

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1706
Author(s):  
Tsvetelina Velikova ◽  
Kalina Tumangelova-Yuzeir ◽  
Ralitsa Georgieva ◽  
Ekaterina Ivanova-Todorova ◽  
Elena Karaivanova ◽  
...  

Probiotics possibly affect local and systemic immune reactions and maintain the intestinal immune homeostasis in healthy individuals and patients with diseases such as irritable bowel syndrome (IBS). In this single-center, blinded trial, we enrolled 40 individuals (20 patients with IBS and 20 healthy individuals) whose blood and fecal samples were collected before and after a 21-day administration of a product comprising Lactobacillus spp., larch arabinogalactan, and colostrum. The percentage of HLA-DR+ natural killer (NK) cells was higher in healthy individuals (p = 0.03) than in patients with IBS after product supplementation. In the fecal samples of patients with IBS, we observed a decline in IL-6, IFN-γ, TNF-α, and secretory IgA levels and, simultaneously, an increase in IL-10 and IL-17A levels after supplementation, although non-significant, whereas, in healthy individuals, we observed a significant decline in IL-6 and IFN-γ levels after supplementation (p < 0.001). Nevertheless, we observed a clinical improvement of symptoms in 65–75% of patients with IBS and the complete resolution of the initial symptoms in five of the 20 patients. We also observed a possible prophylactic effect by the inducing system antiviral impact accompanied by a trend for local immune tolerance in the gut in healthy individuals, where it is the desirable state.

2021 ◽  
Vol 10 (4) ◽  
pp. 875
Author(s):  
Kawaljit Kaur ◽  
Shahram Vaziri ◽  
Marcela Romero-Reyes ◽  
Avina Paranjpe ◽  
Anahid Jewett

Survival and function of immune subsets in the oral blood, peripheral blood and gingival tissues of patients with periodontal disease and healthy controls were assessed. NK and CD8 + T cells within the oral blood mononuclear cells (OBMCs) expressed significantly higher levels of CD69 in patients with periodontal disease compared to those from healthy controls. Similarly, TNF-α release was higher from oral blood of patients with periodontal disease when compared to healthy controls. Increased activation induced cell death of peripheral blood mononuclear cells (PBMCs) but not OBMCs from patients with periodontal disease was observed when compared to those from healthy individuals. Unlike those from healthy individuals, OBMC-derived supernatants from periodontitis patients exhibited decreased ability to induce secretion of IFN-γ by allogeneic healthy PBMCs treated with IL-2, while they triggered significant levels of TNF-α, IL-1β and IL-6 by untreated PBMCs. Interaction of PBMCs, or NK cells with intact or NFκB knock down oral epithelial cells in the presence of a periodontal pathogen, F. nucleatum, significantly induced a number of pro-inflammatory cytokines including IFN-γ. These studies indicated that the relative numbers of immune subsets obtained from peripheral blood may not represent the composition of the immune cells in the oral environment, and that orally-derived immune effectors may differ in survival and function from those of peripheral blood.


Blood ◽  
2009 ◽  
Vol 114 (20) ◽  
pp. 4422-4431 ◽  
Author(s):  
Georg Gruenbacher ◽  
Hubert Gander ◽  
Andrea Rahm ◽  
Walter Nussbaumer ◽  
Nikolaus Romani ◽  
...  

Abstract CD56+ human dendritic cells (DCs) have recently been shown to differentiate from monocytes in response to GM-CSF and type 1 interferon in vitro. We show here that CD56+ cells freshly isolated from human peripheral blood contain a substantial subset of CD14+CD86+HLA-DR+ cells, which have the appearance of intermediate-sized lymphocytes but spontaneously differentiate into enlarged DC-like cells with substantially increased HLA-DR and CD86 expression or into fully mature CD83+ DCs in response to appropriate cytokines. Stimulation of CD56+ cells containing both DCs and abundant γδ T cells with zoledronate and interleukin-2 (IL-2) resulted in the rapid expansion of γδ T cells as well as in IFN-γ, TNF-α, and IL-1β but not in IL-4, IL-10, or IL-17 production. IFN-γ, TNF-α, and IL-1β production were almost completely abolished by depleting CD14+ cells from the CD56+ subset before stimulation. Likewise, depletion of CD14+ cells dramatically impaired γδ T-cell expansion. IFN-γ production could also be blocked by neutralizing the effects of endogenous IL-1β and TNF-α. Conversely, addition of recombinant IL-1β, TNF-α, or both further enhanced IFN-γ production and strongly up-regulated IL-6 production. Our data indicate that CD56+ DCs from human blood are capable of stimulating CD56+ γδ T cells, which may be harnessed for immunotherapy.


Blood ◽  
2000 ◽  
Vol 96 (12) ◽  
pp. 3958-3963 ◽  
Author(s):  
Shigeo Yamashiro ◽  
Ji-Ming Wang ◽  
De Yang ◽  
Wang-Hua Gong ◽  
Hidenobu Kamohara ◽  
...  

Polymorphonuclear leukocytes (PMNLs) are thought to be terminally differentiated, short-lived, and unable to actively synthesize new proteins or to interact with T cells. In the current study, it was found that PMNLs incubated with supernatants of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PHA-sup) expressed high levels of CCR6 mRNA. Neutralization with IgG against several cytokines revealed that tumor necrosis factor (TNF)-α was largely responsible for the PHA-sup–induced CCR6 mRNA expression. Among recombinant cytokines, TNF-α induced high levels of CCR6 mRNA expression, whereas interferon (IFN)-γ induced low levels. The 2 cytokines together exhibited a considerable synergy. Cytokine-activated PMNLs expressed functional CCR6, as detected by the binding of sodium iodide I 125–labeled liver and activation-regulated chemokine (LARC) and dose-dependent migration toward LARC. The induction of CCR6 suggested that these cytokine-activated PMNLs have more similarities with dendritic cells (DCs) that express CCR6 in an immature stage. In fact, the activation of PMNLs with TNF-α and IFN-γ induced the expression of CD83, a dominant cell-surface marker of DCs. When PMNLs were activated with granulocyte macrophage–colony-stimulating factor, TNF-α, and IFN-γ, these cells expressed CD40 and HLA-DR in addition to CD83. Taken together, PMNLs, under appropriate conditions, can undergo a differentiation process characterized by the acquisition of new phenotypes and functions, and such differentiated PMNLs may play more active roles in the adaptive immune response.


1996 ◽  
Vol 1 (5) ◽  
pp. 262-269 ◽  
Author(s):  
PV Byskosh ◽  
AT Reder

IFN-β reduces the number and severity of exacerbations of multiple sclerosis (MS), presumably by modifying immune regulation. We used semiquantitative polymerase chain reaction (RT-PCR) to measure mRNA levels for cytokines before and after IFN β-1b therapy. mRNA was extracted from mononuclear cells of nine healthy controls and 31 patients with MS. Before therapy, IL-10 and leukemia inhibitory factor (UF) mRNA levels were elevated in stable MS compared to active MS. Twenty four hours after IFN β-1b treatment, mRNA levels for IL-1, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNF-α and UF had not changed. At 1 week, TNF-α mRNA increased and IL-10 and UF mRNA rose in 75% of patients. IL-2, IL-4, IL-12, IL-13 and IFN-γ did not change. At 3 months, cytokine mRNA returned to baseline levels. mRNA for the IFN-induced antiviral enzyme, 2, 5-OAS, rose by 24 h, peaked at 1 week, and remained elevated thereafter. Serum triglycerides and liver enzymes rose after therapy. Increased SGPT at 3 months correlated with TNF-α mRNA levels, suggesting that cytokines may cause some side effects of IFN β-1b. Baseline cytokine mRNA levels reflect disease activity, but the therapeutic effect of IFN β-1b does not appear to be explained by changes in cytokine mRNA levels.


2007 ◽  
Vol 292 (3) ◽  
pp. G779-G784 ◽  
Author(s):  
Kevin F. Foley ◽  
Cristen Pantano ◽  
Allison Ciolino ◽  
Gary M. Mawe

Recent studies have shown that mucosal serotonin (5-HT) transporter (SERT) expression is decreased in animal models of colitis, as well as in the colonic mucosa of humans with ulcerative colitis and irritable bowel syndrome. Altered SERT function or expression may underlie the altered motility, secretion, and sensation seen in these inflammatory gut disorders. In an effort to elucidate possible mediators of SERT downregulation, we treated cultured colonic epithelial cells (Caco2) with conditioned medium from activated human lymphocytes. Application of the conditioned medium caused a decrease in fluoxetine-sensitive [3H]5-HT uptake. Individual proinflammatory agents were then tested for their ability to affect uptake. Cells were treated for 48 or 72 h with PGE2 (10 μM), IFN-γ (500 ng/ml), TNF-α (50 ng/ml), IL-12 (50 ng/ml), or the nitric oxide-releasing agent S-nitrosoglutathione (GSNO; 100 μM). [3H]5-HT uptake was then measured. Neither PGE nor IL-12 had any effect on [3H]5-HT uptake, and GSNO increased uptake. However, after 3-day incubation, both TNF-α and IFN-γ elicited significant decreases in SERT function. Neither TNF-α nor IFN-γ were cytotoxic when used for this period of time and at these concentrations. These two cytokines also induced decreases in SERT mRNA and protein levels. By altering SERT expression, TNF-α and IFN-γ could contribute to the altered motility and expression seen in vivo in ulcerative colitis or irritable bowel syndrome.


Blood ◽  
2003 ◽  
Vol 102 (8) ◽  
pp. 2892-2900 ◽  
Author(s):  
Katayoun Rezvani ◽  
Matthias Grube ◽  
Jason M. Brenchley ◽  
Giuseppe Sconocchia ◽  
Hiroshi Fujiwara ◽  
...  

Abstract Antigens implicated in the graft-versus-leukemia (GVL) effect in chronic myeloid leukemia (CML) include WT1, PR1, and BCR-ABL. To detect very low frequencies of these antigen-specific CD8+ T cells, we used quantitative polymerase chain reaction (qPCR) to measure interferon-γ (IFN-γ) mRNA production by peptide-pulsed CD8+ T cells from HLA-A*0201+ healthy volunteers and from patients with CML before and after allogeneic stem cell transplantation (SCT). Parallel assays using cytomegalovirus (CMV) pp65 tetramers demonstrated the IFN-γ copy number to be linearly related to the frequency of tetramer-binding T cells, sensitive to frequencies of 1 responding CD8+ T cell/100 000 CD8+ T cells. Responses to WT1 and PR1 but not BCR-ABL were detected in 10 of 18 healthy donors. Responses to WT1, PR1, or BCR-ABL were observed in 9 of 14 patients with CML before SCT and 5 of 6 after SCT, often to multiple epitopes. Responses were higher in patients with CML compared with healthy donors and highest after SCT. These antigen-specific CD8+ T cells comprised central memory (CD45RO+CD27+CD57–) and effector memory (CD45RO–CD27–CD57+) T cells. In conclusion, leukemia-reactive CD8+ T cells derive from memory T cells and occur at low frequencies in healthy individuals and at higher frequencies in patients with CML. The increased response in patients after SCT suggests a quantitative explanation for the greater effect of allogeneic SCT.


2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Gilson C. Macedo ◽  
Adriana Bozzi ◽  
Helena Rachel Weinreich ◽  
Andre Bafica ◽  
Henrique C. Teixeira ◽  
...  

Tuberculosis remains a major health problem throughout the world causing large number of deaths. Effective disease control and eradication programs require the identification of major antigens recognized by the protective responses againstM. tuberculosis. In this study, we have investigated humoral and cellular immune responses toM. tuberculosis-specific Ag85A, Ag85B, and ESAT-6 antigens in Brazilian patients with pulmonary (P,n=13) or extrapulmonary (EP,n=12) tuberculosis, patients undergoing chemotherapy (PT,n=23), and noninfected healthy individuals (NI,n=7). Compared to NI, we observed increased levels of IgG1 responses to Ag85B and ESAT-6 in P and PT groups. Regarding cellular immunity, Ag85A and ESAT-6 were able to discriminate P, PT, and EP patients from healthy individuals by IFN-γ production and P and PT groups from EP individuals by production of TNF-α. In summary, these findings demonstrate the ability of Ag85A, Ag85B, and ESAT-6 to differentiate TB patients from controls by IgG1, IFN-γ and TNF-α production.


2021 ◽  
Vol 10 (11) ◽  
pp. 2488
Author(s):  
Piotr Marcinowicz ◽  
Magdalena Więdłocha ◽  
Natalia Zborowska ◽  
Weronika Dębowska ◽  
Piotr Podwalski ◽  
...  

Background: Cytokines have a major impact on the neurotransmitter networks that are involved in schizophrenia pathophysiology. First Episode Psychosis (FEP) patients exhibit abnormalities in cytokines levels prior to the start of treatment. Previous studies showed that antipsychotic treatment modulates cytokines levels. The aim of this meta-analysis is to further investigate this relationship. Methods: Several online databases were searched. For meta-analysis of selected studies, we analysed variables containing the number of cases, mean and standard deviation of IL-1β, IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, IFN-γ levels before, and after, antipsychotic treatment. Results: 12 studies were included in the meta-analysis. Our main results demonstrate that, in FEP patients, antipsychotic treatment is related to decreased concentrations of pro-inflammatory IL-1β, IL-6, IFN-γ, TNF-α and anti-inflammatory IL-4, IL-10 cytokines. On the other hand, levels of pro-inflammatory IL-2 and IL-17 remain unaffected. Conclusions: When compared with other meta-analyses of studies involving FEP individuals, results we obtained are consistent regarding decrease in IL-1β, IL-6. Comparing outcomes of our study with meta-analyses of schizophrenic subjects, in general, our results are consistent in IL-1β, IL-6, TNF-α, IFN-γ, IL-2. Our meta-analysis is the only one which indicates a decrease in anti-inflammatory IL-10 in FEP patients after antipsychotic treatment.


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