In vitro assessment of the immunomodulatory effects of multispecies probiotic formulations for management of allergic diseases

2011 ◽  
Vol 2 (3) ◽  
pp. 183-192 ◽  
Author(s):  
N.B.M.M. Rutten ◽  
I. Besseling-Van der Vaart ◽  
M. Klein ◽  
S. De Roock ◽  
A. Vlieger ◽  
...  

Modulation of the composition of the intestinal microbiota with probiotics could possibly offer a way of prevention or management of allergic diseases. The objective of this study was to determine the immunomodulating effects of various multispecies probiotic combinations in vitro, as preamble to application in vivo. Multispecies probiotic combinations were formulated and tested for their effects on in vitro cytokine production by human mononuclear cells and were compared to products that already have shown beneficial effects in vivo. All 4 tested combinations of probiotics showed a 40-71% decrease of Th2 cytokine production (IL-4, IL-5, and IL-13) and a variable increase of Th1 (IFN-γ) and Treg cytokine (IL-10) production compared to the medium. A specific probiotic mixture that contained Bifidobacterium breve W25, Bifidobacterium lactis ATCC SD 5219, B. lactis ATCC SD 5220, Lactobacillus plantarum W62, Lactobacillus salivarius W57 and Lactococcus lactis W19 was superior in its stimulating effect on IL-10 production (significant better than the other tested combinations; P=0.001). Modulation of in vitro cytokine production profiles can be used to differentiate between selected probiotic formulations for their immunomodulatory properties. In the future it should be demonstrated whether the immunomodulatory capacities from the multispecies probiotic formulation with the desired profile will be effective in vivo (in adolescents, followed by application in children).

2000 ◽  
Vol 7 (4) ◽  
pp. 669-675 ◽  
Author(s):  
Maribel G. Vallespi ◽  
Luis A. Glaria ◽  
Osvaldo Reyes ◽  
Hilda E. Garay ◽  
Joel Ferrero ◽  
...  

ABSTRACT Previous studies have shown that cyclic peptides corresponding to residues 35 to 52 of the Limulus antilipopolysaccharide (anti-LPS) factor (LALF) bind and neutralize LPS-mediated in vitro and in vivo activities. Therapeutic approaches based on agents which bind and neutralize LPS activities are particularly attractive because these substances directly block the primary stimulus for the entire proinflammatory cytokine cascade. Here we describe new activities of the LALF31–52 peptide, other than its LPS binding ability. Surprisingly, supernatants from human mononuclear cells stimulated with the LALF peptide are able to induce in vitro antiviral effects on the Hep-2 cell line mediated by gamma interferon (IFN-γ) and IFN-α. Analysis of the effect of LALF31–52 on tumor necrosis factor (TNF) and nitric oxide (NO) production by LPS-stimulated peritoneal macrophages revealed that a pretreatment with the peptide decreased LPS-induced TNF production but did not affect NO generation. This indicates that the LALF peptide modifies the LPS-induced response. In a model in mice with peritoneal fulminating sepsis, LALF31–52 protected the mice when administered prophylactically, and this effect is related to reduced systemic TNF-α levels. This study demonstrates, for the first time, the anti-inflammatory properties of the LALF-derived peptide. These properties widen the spectrum of the therapeutic potential for this LALF-derived peptide and the molecules derived from it. These agents may be useful in the prophylaxis and therapy of viral and bacterial infectious diseases, as well as for septic shock.


Marine Drugs ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. 702
Author(s):  
Tauseef Ahmad ◽  
Mathew Suji Eapen ◽  
Muhammad Ishaq ◽  
Ah Young Park ◽  
Samuel S. Karpiniec ◽  
...  

Fucoidans are sulfated, complex, fucose-rich polymers found in brown seaweeds. Fucoidans have been shown to have multiple bioactivities, including anti-inflammatory effects, and are known to inhibit inflammatory processes via a number of pathways such as selectin blockade and enzyme inhibition, and have demonstrated inhibition of inflammatory pathologies in vivo. In this current investigation, fucoidan extracts from Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica were assessed for modulation of pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-6) by human peripheral blood mononuclear cells (PBMCs) and in a human macrophage line (THP-1). Fucoidan extracts exhibited no signs of cytotoxicity in THP-1 cells after incubation of 48 h. Additionally, all fucoidan extracts reduced cytokine production in LPS stimulated PBMCs and human THP-1 cells in a dose-dependent fashion. Notably, the 5–30 kDa subfraction from Macrocystis pyrifera was a highly effective inhibitor at lower concentrations. Fucoidan extracts from all species had significant anti-inflammatory effects, but the lowest molecular weight subfractions had maximal effects at low concentrations. These observations on various fucoidan extracts offer insight into strategies that improve their efficacy against inflammation-related pathology. Further studies should be conducted to elucidate the mechanism of action of these extracts.


1989 ◽  
Vol 17 (01n02) ◽  
pp. 45-50 ◽  
Author(s):  
Yasuo Tanno ◽  
Yuriko Shindoh ◽  
Tamotsu Takishima

Our previous study showed the inhibitory effect of Qing-Fei-Tang (Q.T.F.) and baicalein on the leukotriene (LT)B4 synthesis of human alveolar macrophages. It has recently been demonstrated that LTs support various cell growth, and basophil and its precursor numbers increase in atopic patients. Therefore, we examined the effect of anti-allergic drugs, including Q.F.T., Xiao-Qing-Long-Tang (X.Q.L.T.), Chai-Pu-Tang (C.P.T.), baicalein and ketotifen which have been used for treatment of bronchial asthma, on human basophil growth in vitro using cord blood mononuclear cells as a basophil precursor source and conditioned medium of T cell leukemia cell line Mo as a growth factor. Two-week cultured basophil numbers identified by alcian blue-safranin staining and those histamine contents assayed fluorometrically were inhibited by Q.F.T. (1.0 mg/ml), X.Q.L.T. (0.01–1.0 mg/ml), C.P.T. (0.01–1.0 mg/ml), baicalein (1–100 μM) or ketotifen (1–100 μM) in a dose-dependent manner while low dose (0.01–0.1 mg/ml) of Q.F.T. showed an enhancing effect on the basophil growth and the histamine content. However, LTB4 or LTC4 failed in restoring the basophil growth reduced by 1 mg/ml of C.P.T. or 100 μM of ketotifen. These results suggest that anti-allergic drugs may modulate basophil growth and differentiation in vitro and/or in vivo and therefore by useful and reasonable for controlling allergic diseases including bronchial asthma.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2659-2659
Author(s):  
Edna Ku ◽  
JianXiang Zou ◽  
Fanqi Bai ◽  
Jeffrey S. Painter ◽  
Alan F. List ◽  
...  

Abstract Background: The myelodysplastic syndromes (MDS) comprise a spectrum of stem cell malignancies with natural histories that vary from indolent mild cytopenias to rapid transformation to acute leukemia. MDS patients have impaired T cell antigen-induced proliferation and reduced T helper-1 (Th-1) cytokine production. Lenalidomide, an immuno-modulatory drug structurally-related to thalidomide, is FDA-approved for the treatment of MDS with chromosome 5q deletion; however, its mechanism of action is not fully characterized. We hypothesize that immune modulation by lenalidomide will be an effective adjunct to vaccine therapy for patients with MDS. Methods: The immunoregulatory effects of lenalidomide were investigated both in vitro and in vivo. Peripheral blood mononuclear cells (PBMCs) from MDS patients and normal controls were stimulated with anti-CD3 cross-linking, allogeneic dendritic cells (allo-DCs), autologous dendritic cells (auto-DCs), and patient-derived autologous bone marrow mononuclear cells (BM-MNC) as antigen sources in the presence of DMSO (vehicle control) and lenalidomide [0.625 μM to 40 μM]. Proliferation of specific CD4+ and CD8+ T cell populations was assessed by Brdu incorporation and intracellular cytokine production by flow cytometry. Preliminary studies were performed to examine the combined effects of the GMCSF/K562 “bystander” vaccine (gift of Dr. I. Borrello, Johns Hopkins University) and lenalidomide on antigen-induced T cell proliferation in PBMC from both normal donors and MDS patients. Results: Lenalidomide augmented a Th-1-biased cytokine (IFN-γ, TNF-α and IL-2) response from normal donors (n=5) and MDS patients (n=5). The Th-1-biased increase in cytokine production accompanied erythroid response in MDS patients treated with 10 mg of lenalidomide for 16 weeks (n=4 responders and 3 non-responders) (List et al, NEJM2005;351:549). Augmentation of antigen-dependent proliferation accompanied cytokine responses both in vitro and in vivo. Next, we examined the effects of lenalidomide on in vitro response to autologous and allogeneic antigens. We found that pre-treatment T cell proliferation in response to auto-DC priming was not distinguishable from background. However, proliferation in response to auto-BM-MNCs used as a source of autologous tumor antigens was significantly increased by lenalidomide in CD3+, CD4+, and CD8+ T cell populations (P=0.002, 0.04, and 0.04, respectively). Proliferation after allo-DC exposure was also significantly enhanced by lenalidomide treatment (P<0.05). GMCSF/K562 “bystander” vaccine-increased proliferation to allo-DC antigens in CD4+ and CD8+ T cells without exposure to lenalidomide (n=4) (167% increase vs. 245% increase, respectively). When allo-DC-stimulated PBMCs were treated with lenalidomide alone, CD4+ and CD8+ proliferation was increased by 47% and 39% respectively. The combination of lenalidomide and the GMCSF/K562 vaccine further enhanced T cell proliferation to allo-DC stimulation (325% and 397% for CD4+ and CD8+ populations, respectively). Conclusion: Lenalidomide significantly augments T cell immune function in MDS, and potentiates immune response to the GMCSF/K562 “bystander” vaccine. We conclude that lenalidomide represents an attractive adjunct to vaccines for clinical investigation in MDS.


2004 ◽  
Vol 74 (4) ◽  
pp. 279-284 ◽  
Author(s):  
Rühl ◽  
Garcia ◽  
Schweigert ◽  
Worm

Retinoids modulate many physiological processes such as the differentiation and growth of different cell types, including cells from the immune system. We have previously shown that retinoids modulate IgE production in vitro and in vivo. In the present study we investigated the effects of retinoids in non-sensitized and ovalbumin-sensitized mice that were fed for 11 weeks with three different vitamin A (VA) diets: a) VA-deficiency diet, b) base diet, and c) base diet supplemented with 0.5% all-trans-retinoic acid (ATRA). Phorbol-myristate-acetate (PMA)/ionomycin-stimulated SMC (splenic mononuclear cells) from mice fed with ATRA and the vitamin A-deficient diet group showed increased interleukin-4 (IL-4) responses in non-sensitized mice. After ovalbumin sensitization in the VA-deficient and the ATRA supplementation diet groups, no significant effects on IL-4 production were observed. By contrast, gamma interferon (IFN-gamma production from PMA/ionomycin-stimulated SMC was enhanced in the VA-deficient diet group in ovalbumin-sensitized mice, and also in non-sensitized mice compared to the base and the ATRA-supplemented diet group. The data indicate that VA and retinoid content in a diet influences the cytokine response in non-sensitized and also ovalbumin-sensitized mice. Therefore these molecules may serve as active modulators of cytokine production in vivo that are responsible for the induction and persistence of atopic diseases.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Rajesh Mandarapu ◽  
Rajanna Ajumeera ◽  
Vijayalakshmi Venkatesan ◽  
Balakrishna Murthy Prakhya

In recent times, human cell-based assays are gaining attention in assessments of immunomodulatory effects of chemicals. In the study here, the possible effects of cypermethrin and mancozeb on lymphocyte proliferation and proinflammatory (tumor necrosis factor (TNF-)α) and immunoregulatory cytokine (interferon- (IFN-)γ, interleukins (IL) 2, 4, 6, and 10) formationin vitrowere investigated. Human peripheral blood mononuclear cells (PBMC) were isolated and exposed for 6 hr to noncytotoxic doses (0.45–30 µM) of cypermethrin or mancozeb in the presence of activating rat S9 fraction. Cultures were then further incubated for 48 or 72 hr in fresh medium containing phytohemagglutinin (10 µg/mL) to assess, respectively, effects on cell proliferation (BrdU-ELISA method) and cytokine formation (flow cytometric bead immunoassays). Mancozeb induced dose-dependent increases in lymphocyte proliferation, inhibition of production of TNFαand theTH2 cytokines IL-6 and IL-10, and an increase in IFNγ(TH1 cytokine) production (at least 2-fold compared to control); mancozeb also induced inhibition of IL-4 (TH2) and stimulated IL-2 (TH1) production, albeit only in dose-related manners for each. In contrast, cypermethrin exposure did not cause significant effects on proliferation or cytokine profiles. Further studies are needed to better understand the functional significance of ourin vitrofindings.


2008 ◽  
Vol 60 (7) ◽  
pp. 901-907 ◽  
Author(s):  
Hee Kang ◽  
Yoo-Joung Oh ◽  
Ho-Young Choi ◽  
In-Hye Ham ◽  
Hyun-Su Bae ◽  
...  

2000 ◽  
Vol 68 (3) ◽  
pp. 1014-1018 ◽  
Author(s):  
Fanny N. Lauw ◽  
Tessa ten Hove ◽  
Pascale E. P. Dekkers ◽  
Evert de Jonge ◽  
Sander J. H. van Deventer ◽  
...  

ABSTRACT Endotoxin (lipopolysaccharide [LPS]) tolerance is characterized by a reduced capacity of monocytes to produce proinflammatory cytokines upon restimulation in vitro. To determine whether LPS exposure induces a change in lymphocyte cytokine production and whether this results in a shift in the T-helper 1 (Th1)/Th2 balance, whole blood obtained from seven healthy subjects before and after an intravenous injection of LPS (4 ng/kg) was stimulated in vitro with the T-cell stimulus anti-CD3/CD28 or staphylococcal enterotoxin B. Whole-blood production of the Th1 cytokines gamma interferon (IFN-γ) and interleukin-2 (IL-2) was markedly reduced at 3 and 6 h, while the production of the Th2 cytokines IL-4 and IL-5 was not influenced or was slightly increased. The IFN-γ/IL-4 ratio was strongly decreased at 6 h. Serum obtained after LPS exposure could slightly inhibit the release of IFN-γ but increased IL-4 production during stimulation of blood drawn from subjects not previously exposed to LPS. Normal serum also inhibited IFN-γ production, albeit to a lesser extent. LPS exposure influences lymphocyte cytokine production, resulting in a shift toward a Th2 cytokine response, an effect that may be mediated in part by soluble factors present in serum after LPS administration in vivo.


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