Effect of calcitriol on in vitro whole blood cytokine production in critically ill dogs

2018 ◽  
Vol 236 ◽  
pp. 31-36 ◽  
Author(s):  
J.A. Jaffey ◽  
J. Amorim ◽  
A.E. DeClue
1998 ◽  
Vol 42 (7) ◽  
pp. 1605-1609 ◽  
Author(s):  
Marc J. Schultz ◽  
Peter Speelman ◽  
Sebastian Zaat ◽  
Sander J. H. van Deventer ◽  
Tom van der Poll

ABSTRACT To determine the effects of penicillin and erythromycin on cytokine production induced by heat-killed Streptococcus pneumoniae (HKSP), we studied the effects of those drugs on cytokine production induced by S. pneumoniaein human whole blood in vitro and ex vivo. In whole blood in vitro, erythromycin, but not penicillin, caused a dose-dependent decrease in HKSP-induced production of tumor necrosis factor alpha (TNF) and interleukin 6 (IL-6), while the production of IL-10, IL-12, and gamma interferon was inhibited only at the highest erythromycin concentration tested (10−3 M). The production of TNF and IL-6 in whole blood obtained from healthy subjects after a 30-min infusion of erythromycin (1,000 mg) was lower after ex vivo stimulation with HKSP than that in blood drawn before the infusion. Inhibition of TNF contributed to erythromycin-induced inhibition of IL-6 synthesis. Inhibition of TNF and IL-6 production by erythromycin may have a negative impact on host defense mechanisms during pneumococcal pneumonia.


Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 103
Author(s):  
Lluis Rodas ◽  
Sonia Martínez ◽  
Aina Riera-Sampol ◽  
Hannah J. Moir ◽  
Pedro Tauler

Immune system functionality has been commonly assessed by a whole-blood or isolated-cell stimulation assay. The aim of this study was to determine whether cytokine production in whole-blood-stimulated samples is influenced by age, sex, and smoking. A descriptive cross-sectional study in 253 healthy participants aged 18–55 years was conducted. Whole blood samples were stimulated for 24 h with LPS and concentrations of IL-6, IL-10, and TNF-α were determined in the culture media. Among parameters considered, statistical regression analysis indicated that smoking (change in R2 = 0.064, p < 0.001) and sex (change in R2 = 0.070, p < 0.001) were the main predictors for IL-10 production, with higher values for women and non-smokers. Age was also found to be a significant predictor (change in R2 = 0.021, p < 0.001), with higher values for younger ages. Age (change in R2 = 0.089, p = 0.013) and smoking (change in R2 = 0.037, p = 0.002) were found to be negative predictors for IL-6 production. Regarding TNF-α-stimulated production, age (change in R2 = 0.029, p = 0.009) and smoking (change in R2 = 0.022, p = 0.022) were found to be negative predictors. Furthermore, sex (change in R2 = 0.016, p = 0.045) was found to be a significant predictor, with lower values for women. In conclusion, sex, age, and smoking were found to be independent determinants of stimulated cytokine production. While female sex is associated with higher IL-10 and lower TNF-α production, aging and smoking are associated with lower IL-6, IL-10, and TNF-α production.


1999 ◽  
Vol 89 (3) ◽  
pp. 665 ◽  
Author(s):  
Takashi Kawasaki ◽  
Masanori Ogata ◽  
Chika Kawasaki ◽  
Jun-ichi Ogata ◽  
Yoshitaka Inoue ◽  
...  

2008 ◽  
Vol 76 (7) ◽  
pp. 3156-3163 ◽  
Author(s):  
Kim Jemmett ◽  
Annalisa Macagno ◽  
Monica Molteni ◽  
John E. Heckels ◽  
Carlo Rossetti ◽  
...  

ABSTRACT Septicemia caused by Neisseria meningitidis is characterized by increasing levels of meningococcal lipopolysaccharide (Nm-LPS) and cytokine production in the blood. We have used an in vitro human whole-blood model of meningococcal septicemia to investigate the potential of CyP, a selective Toll-like receptor 4 (TLR4)-MD-2 antagonist derived from the cyanobacterium Oscillatoria planktothrix FP1, for reducing LPS-mediated cytokine production. CyP (≥1 μg/ml) inhibited the secretion of the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1β (IL-1β), and IL-6 (by >90%) and chemokines IL-8 and monocyte chemoattractant protein 1 (by ∼50%) induced by the treatment of blood with pure Nm-LPS, by isolated outer membranes, and after infection with live meningococci of different serogroups. In vitro studies with human dendritic cells and TLR4-transfected Jurkat cells demonstrated that CyP competitively inhibited Nm-LPS interactions with TLR4 and subsequent NF-κB activation. These data demonstrate that CyP is a potent antagonist of meningococcal LPS and could be considered a new adjunctive therapy for treating septicemia.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Cheng-Shiun He ◽  
William D. Fraser ◽  
Michael Gleeson

Aim. Our aims were to determine the influence of plasma total 25-hydroxy vitamin D (25(OH)D) status on the plasma cytokine concentrations in athletes and the in vitro effects of different doses of 1, 25 dihydroxyvitamin D3 (1, 25(OH)2D3) on multiantigen stimulated cytokine production by whole blood and peripheral blood mononuclear cell (PBMC) cultures. Methods. Plasma samples from 43 athletes with high and low levels of 25(OH)D were assayed for the concentrations of cytokines. The whole blood samples and PBMCs from healthy subjects were incubated in vitro with a multi-antigen vaccine and different doses of added 1, 25(OH)2D3. The circulating cytokines and stimulated whole blood and PBMC culture production of cytokines were determined using a biochip assay. Results. The circulating interleukin-(IL-)10 and interferon-(IFN-) γ concentrations were significantly higher in the vitamin D sufficient athletes. Furthermore, the production of tumour necrosis factor-(TNF-) α, IL-6, IFN-γ, IL-2, and IL-10 by whole blood culture was significantly inhibited by 1, 25(OH)2D3 concentrations of 1000 pmol/L or 10000 pmol/L. Conclusions. We found that the influence of vitamin D on circulating cytokines might be different in athletes compared with nonathletes and cytokines production by whole blood culture was not influenced by 1, 25(OH)2D3 in concentrations within the normal healthy range.


2018 ◽  
Vol 2 (18) ◽  
pp. 2296-2306 ◽  
Author(s):  
Ruqayyah J. Almizraq ◽  
Philip J. Norris ◽  
Heather Inglis ◽  
Somaang Menocha ◽  
Mathijs R. Wirtz ◽  
...  

AbstractTransfusion of red cell concentrates (RCCs) is associated with increased risk of adverse outcomes that may be affected by different blood manufacturing methods and the presence of extracellular vesicles (EVs). We investigated the effect of different manufacturing methods on hemolysis, residual cells, cell-derived EVs, and immunomodulatory effects on monocyte activity. Thirty-two RCC units produced using whole blood filtration (WBF), red cell filtration (RCF), apheresis-derived (AD), and whole blood–derived (WBD) methods were examined (n = 8 per method). Residual platelet and white blood cells (WBCs) and the concentration, cell of origin, and characterization of EVs in RCC supernatants were assessed in fresh and stored supernatants. Immunomodulatory activity of RCC supernatants was assessed by quantifying monocyte cytokine production capacity in an in vitro transfusion model. RCF units yielded the lowest number of platelet and WBC-derived EVs, whereas the highest number of platelet EVs was in AD (day 5) and in WBD (day 42). The number of small EVs (&lt;200 nm) was greater than large EVs (≥200 nm) in all tested supernatants, and the highest level of small EVs were in AD units. Immunomodulatory activity was mixed, with evidence of both inflammatory and immunosuppressive effects. Monocytes produced more inflammatory interleukin-8 after exposure to fresh WBF or expired WBD supernatants. Exposure to supernatants from AD and WBD RCC suppressed monocyte lipopolysaccharide-induced cytokine production. Manufacturing methods significantly affect RCC unit EV characteristics and are associated with an immunomodulatory effect of RCC supernatants, which may affect the quality and safety of RCCs.


1999 ◽  
Vol 89 (3) ◽  
pp. 665 ◽  
Author(s):  
Takashi Kawasaki ◽  
Masanori Ogata ◽  
Chika Kawasaki ◽  
Jun-ichi Ogata ◽  
Yoshitaka Inoue ◽  
...  

2002 ◽  
Vol 18 (1) ◽  
pp. 15-27 ◽  
Author(s):  
Inge M Wouters ◽  
Jeroen Douwes ◽  
Peter S Thorne ◽  
Dick Heederik ◽  
Gert Doekes

Inflammatory airway responses to bioaerosols and to their active compounds, such as endotoxin and β(1 → 3)- glucan, vary between individuals. These differences may be explained by variation in cytokine responsiveness, which can be assessed by in vitro stimulation tests with isolated blood leukocytes or lung macrophages. In large- scale population studies, ex vivo induced cytokine production may also be tested with a more simple `whole blood assay’ (WBA). However, applicability of a WBA to characterize a subject’s responsiveness depends largely on its reproducibility. This study was conducted to: 1) assess the within- and between-subject variability in cytokine production in a WBA after stimulation with endotoxin or β(1 → 3)-glucan; and 2) to determine under which conditions this test is most discriminating between subjects and most reproducible within subjects. Blood was collected from 14 healthy volunteers, of whom 10 also participated on a second occasion. Each blood sample was used in two WBA tests; the first WBA was initiated two hours and the second 26 hours after venapuncture. The WBA test itself comprised overnight incubation with serial dilutions of endotoxin [lipopolysaccharide (LPS)] and curdlan (a β(1 → 3)-glucan), after which blood cell supernatant was collected. Interleukin(IL)-1, IL6, IL8 and tumor necrosis factor (TNF) were determined in the supernatant. In all individuals, a dose-dependent production of cytokines was observed for both LPS and curdlan. For all cytokines, variation between subjects was higher than within subjects, and this was most pronounced for IL1 and IL6. There was moderate-to-high correlation in the induced release of all four cytokines, and between cytokine release induced by LPS or curdlan. Optimal stimulation concentrations were 6.25 and 12.5 ng/mL for endotoxin and 12 500 and 25 000 ng/mL for curdlan. Cytokine production in WBA initiated 26 hours after venapuncture showed lower between-subject and larger within-subject variance, thus favoring an early initiation of the assay. In conclusion, measuring endotoxin-or glucan-induced cytokine production in a WBA initiated within two hours after venapuncture appears to be an effective method to determine a person’s cytokine responsiveness, at least in healthy naive subjects. Toxicology and Industrial Health 2002; 18: 15-27.


1997 ◽  
Vol 41 (7) ◽  
pp. 1439-1443 ◽  
Author(s):  
J T Frieling ◽  
J A Mulder ◽  
T Hendriks ◽  
J H Curfs ◽  
C J van der Linden ◽  
...  

The in vitro production of interleukin-1beta (IL-1beta), IL-6, and the IL-1 receptor antagonist (IL-1ra) in whole blood upon stimulation with different bacterial strains was measured to study the possible relationship between disease severity and the cytokine-inducing capacities of these strains. Escherichia coli, Neisseria meningitidis, Neisseria gonorrhoeae, Bacteroides fragilis, Capnocytophaga canimorsus, Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Streptococcus pyogenes induced the cytokines IL-1beta, IL-6, and IL-1ra. Gram-negative bacteria induced significantly higher levels of proinflammatory cytokine production than gram-positive bacteria. These differences were less pronounced for the anti-inflammatory cytokine IL-1ra. In addition, blood was stimulated with E. coli killed by different antibiotics to study the effect of the antibiotics on the cytokine-inducing capacity of the bacterial culture. E. coli treated with cefuroxime and gentamicin induced higher levels of IL-1beta and IL-6 production but levels of IL-1ra production similar to that of heat-killed E. coli. In contrast, ciprofloxacin- and imipenem-cilastatin-mediated killing showed a decreased or similar level of induction of cytokine production as compared to that by heat-killed E. coli; polymyxin B decreased the level of production of the cytokines.


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