scholarly journals Effects of FR-91 on Immune Cells from Healthy Individuals and from Patients with Non-Hodgkin Lymphoma

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
V. R. M. Lombardi ◽  
E. Martínez ◽  
R. Chacón ◽  
I. Etcheverría ◽  
R. Cacabelos

The immune system is subject to destruction and dysfunction as a result of attacks by pathogenic and environmental agents. In addition, many clinical situations exist in which it is desirable to stimulate or suppress the immune system. The present study evaluated the screening efficacy of flow cytometric lymphocyte subset typing in peripheral blood mononuclear cells from healthy individuals (HI) and from patients with non-Hodgkin lymphoma (NHL) treated with different concentrations of FR-91, a standardized lysate of microbial cells belonging to the Bacillus genus, andin vitrocytokine production. Increased expression of subset markers (CD3, CD4, CD8) in NHL and CD3 in HI suggests an immunomodulating effect of FR-91. In addition the results of cytokine production also demonstrated a clear effect of FR-91 on both populations. A significant increase of IL-6, IL-12, IFN-γand TNF-αwas observed in the HI group after treatment with FR-91. In a similar manner an increase of IL-2, IL-6, IL-12, IFN-γand TNF-αwas also observed in the NHL group. In conclusion FR-91 seems to affect lymphocyte subpopulations,in vitrocytokine production, as well as mitogen-induced lymphocyte activation in a dose-dependent manner in both healthy individuals and NHL patients.

2013 ◽  
Vol 4 (4) ◽  
pp. 313-317 ◽  
Author(s):  
N.J. Hepburn ◽  
I. Garaiova ◽  
E.A. Williams ◽  
D.R. Michael ◽  
S. Plummer

The objective of this study was to examine the effect of daily probiotic supplementation upon the immune profile of healthy participants by the assessment of ex vivo cytokine production. Twenty healthy adult volunteers received a multi-strain probiotic supplement consisting of two strains of Lactobacillus acidophilus (CUL60 and CUL21), Bifidobacterium lactis (CUL34) and Bifidobacterium bifidum (CUL20) and fructooligosaccharide for 12 weeks. Blood samples were collected at baseline, 6 and 12 weeks. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured ex vivo in the presence or absence of lipopolysaccharide and cytokine production was assessed. Postintervention, a significant decrease in the production of interleukin-6 and interleukin-1β was apparent when PBMCs were incubated in the presence of lipopolysaccharide, whilst a significant increase in IL-10 and transforning growth factor-β production was seen when the cells were incubated without an additional stimulus. This preliminary study demonstrates the potential of a multi-strain probiotic supplement to alter the immune response as demonstrated by changes in ex vivo cytokine production. Such results demonstrate the potential benefit of probiotic supplementation for healthy individuals and warrants further investigation.


Cytokine ◽  
2016 ◽  
Vol 88 ◽  
pp. 184-192 ◽  
Author(s):  
Hélio Galdino ◽  
Rodrigo Saar Gomes ◽  
Jessica Cristina dos Santos ◽  
Lívia Lara Pessoni ◽  
Anetícia Eduarda Maldaner ◽  
...  

1998 ◽  
Vol 21 (5) ◽  
pp. 269-273 ◽  
Author(s):  
B.L. Jaber ◽  
S. Sundaram ◽  
M. Cendoroglo Neto ◽  
A.J. King ◽  
B.J.G. Pereira

Gram-negative bacterial lipopolysaccharide (LPS) is a well known stimulus for cytokine production, particularly interleukin-1 (IL-1) and tumor necrosis tactor alpha (TNFα). Polymyxin B (PMX-B) is a cationic polypeptide that binds to LPS, neutralizing its biological effects. PMX-B also disrupts gram-negative bacterial cell membrane phospholipids but is highly toxic to mammalian cells, therefore is of limited use. PMX-B is used as additive to media, as a way to handle LPS contamination. To derive benefit from the ability of PMX-B to neutralize lipid A in vivo while avoiding its systemic toxicity, PMX-B was covalently bound to polystyrene-derivative fibers, creating a hemoperfusion column (PMX-F) for the selective removal of circulating ET In vitro PMX-F hemoperfusion studies have demonstrated effective ET removal, using either the Limulus amebocyte lysate assay or TNFα production by peripheral blood mononuclear cells (PBMC) as an index of ET removal. However, the question whether PMX-B itself could stimulate human PBMC to produce cytokines has not been adequately addressed. We examined the effect of increasing concentrations of PMX-B on cytokine production by PBMC in vitro. PBMC harvested from healthy volunteers were incubated for 24 hours at 37°C with control (tissue culture media RPMI), or 5 µg/ml, 10 µg/ml, 20 µg/ml or 100 µg/ml PMX-B. At the end of 24 hours, PBMC were subjected to three freeze-thaw cycles, and total TNFα production (pg/2.5x106 PBMC) was measured by radioimmunoassay. Total TNFα production by PBMC was 163 ± 3 pg, 171 ± 9 pg, 164 ± 4 pg, 323 ± 63 pg and 331 ± 58 pg, in the control, PMX-B 5 µg/ml, 10 µg/ml, 20 µg/ml and 100 µg/ml conditions, respectively. Compared to controls (RPMI), the percentage increase in TNFα production by PBMC was 5 ± 6% (P=0.23), 1 ± 3% (P=0.45), 99 ± 40% (P=0.03) and 103 ± 36% (P=0.02) in the presence of 5 µg/ml, 10 µg/ml, 20 µg/ml and 100 µg/ml of PMX-B, respectively. Furthermore, total TNFα production correlated significantly with increasing concentrations of PMX-B (R=0.53, P=0.007). We conclude that the use of PMX-B in in vitro studies as an LPS-neutralizing agent, or in the experimental treatment of endotoxic or septic shock can lead to erroneous interpretations of cytokine production by PBMC, and should be used cautiously in in vitro systems at high concentrations.


Blood ◽  
1989 ◽  
Vol 74 (8) ◽  
pp. 2713-2717 ◽  
Author(s):  
W Hinterberger ◽  
G Adolf ◽  
P Bettelheim ◽  
K Geissler ◽  
C Huber ◽  
...  

Abstract The production of interferons (IFNs), IFN-gamma, tumor necrosis factors (TNFs) and TNF-alpha (TNF-alpha) by peripheral blood mononuclear cells (PBMNCs) of untransfused and transfused, but otherwise untreated patients with severe aplastic anemia (SAA) was determined using bioassays and immunoassays. In untransfused and pretransfused SAA patients, spontaneous and lectin-induced production of these cytokines by PBMNCs was strongly enhanced. Cytokine production in untransfused SAA patients did not differ from that in pretransfused patients. Similar relative frequencies of activated (HLA-DR+) lymphocyte subpopulations present in the PBMNCs demonstrated cytokine overproduction per cells. Cytokine production was studied in three SAA patients before and after blood cell transfusions. Spontaneous and lectin-induced production of these cytokines was abnormally high and unaffected by blood transfusions. In another patient exhibiting abnormal cytokine production, the hematopoietic response to cyclosporin- A in vivo was accompanied by normalization of cytokine production in vitro. We conclude that overproduction of IFN-gamma and TNF-alpha by lectin-stimulated PBMNCs is an intrinsic abnormality of SAA unrelated to blood transfusions. Normalization of production of IFN-gamma and TNF- alpha accompanying a clinical response to cyclosporin-A may cautiously be taken as further evidence suggesting a pathogenetic role of cytokine overproduction in SAA.


2009 ◽  
Vol 77 (9) ◽  
pp. 3826-3837 ◽  
Author(s):  
Anna Martner ◽  
Susann Skovbjerg ◽  
James C. Paton ◽  
Agnes E. Wold

ABSTRACT Streptococcus pneumoniae is a major pathogen in humans. The pathogenicity of this organism is related to its many virulence factors, the most important of which is the thick pneumococcal capsule that minimizes phagocytosis. Another virulence-associated trait is the tendency of this bacterium to undergo autolysis in stationary phase through activation of the cell wall-bound amidase LytA, which breaks down peptidoglycan. The exact function of autolysis in pneumococcal pathogenesis is, however, unclear. Here, we show the selective and specific inefficiency of wild-type S. pneumoniae for inducing production of phagocyte-activating cytokines in human peripheral blood mononuclear cells (PBMC). Indeed, clinical pneumococcal strains induced production of 30-fold less tumor necrosis factor (TNF), 15-fold less gamma interferon (IFN-γ), and only negligible amounts of interleukin-12 (IL-12) compared with other closely related Streptococcus species, whereas the levels of induction of IL-6, IL-8, and IL-10 production were similar. If pneumococcal LytA was inactivated by mutation or by culture in a medium containing excess choline, the pneumococci induced production of significantly more TNF, IFN-γ, and IL-12 in PBMC, whereas the production of IL-6, IL-8, and IL-10 was unaffected. Further, adding autolyzed pneumococci to intact bacteria inhibited production of TNF, IFN-γ, and IL-12 in a dose-dependent manner but did not inhibit production of IL-6, IL-8, and IL-10 in response to the intact bacteria. Fragments from autolyzed bacteria inhibited phagocytosis of intact bacteria and reduced the in vitro elimination of pneumococci from human blood. Our results suggest that fragments generated by autolysis of bacteria with reduced viability interfere with phagocyte-mediated elimination of live pneumococci.


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