Effect of pro-inflammatory cytokines on spontaneous apoptosis in leukocyte sub-sets within a whole blood culture

Cytokine ◽  
2005 ◽  
Vol 31 (2) ◽  
pp. 161-167 ◽  
Author(s):  
J MCNAMEE ◽  
P BELLIER ◽  
B KUTZNER ◽  
R WILKINS
2021 ◽  
Author(s):  
Stephania Vazquez-Rodriguez ◽  
Lourdes A. Arriaga-Pizano ◽  
Ismael Mancilla-Herrera ◽  
Jessica Prieto-Chávez ◽  
Roberto Arizmendi-Villanueva ◽  
...  

AbstractObjectiveThe use of intravenous human immunoglobulin (IVIg) as adjuvant therapy for sepsis has been shown efficacious in adults, but its use in pregnant women and newborns is controversial. Fc gamma receptors (FcγRs) support the ability of IVIg to stimulate the synthesis of inflammatory mediators and promote phagocytosis by leukocytes, however, the FcγRs expression is differential between adults and neonates. We aimed to explore the effect of IVIg in monocytes and neutrophils from mother and neonates in whole blood cultures.Study designWhole blood from adults, maternal, and neonates were incubated with LPS and/or IVIg. After 0, 24, and 48 hours, we measured the expression of FcγRs (CD16, CD32, and CD64) and bacterial phagocytosis by monocytes and neutrophils. Also, the concentration of pro-inflammatory cytokines/chemokines was determined.ResultsFcγRs expression is quite similar among groups, and the LPS or IVIg challenge did not change the FcγRs expression on monocytes and neutrophils. Also, the LPS or IVIg challenge did not modify phagocytosis capacity in any group. However, IVIg induces a higher IL-8 response in neonates than in adults.ConclusionOur results suggest that the IL-8 response to IVIg in whole blood from neonates is not dependent on differential FcγR expression.Key messagesIVIg challenge in neonates or adults does not induce FcγR change expression on monocytes or neutrophilsIVIg induces higher IL-8 response in neonates than in adults


2004 ◽  
Vol 32 (3) ◽  
pp. 489-492 ◽  
Author(s):  
S.W. Edwards ◽  
M. Derouet ◽  
M. Howse ◽  
R.J. Moots

Neutrophils rapidly undergo spontaneous apoptosis, but this process can be considerably delayed by exposure to a variety of agents such as pro-inflammatory cytokines. The anti-apoptotic protein of the Bcl-2 family, Mcl-1, plays a key role in the regulation of neutrophil apoptosis. The protein has some unusual properties compared with other family members, including an extremely high turnover rate. Many factors, such as cytokines and local oxygen concentrations, can regulate cellular levels of Mcl-1 via transcription and post-transcriptional modification, control the survival time of neutrophils within tissues and thereby influence the inflammatory response.


Author(s):  
Xavier Roblin ◽  
Adrian Serone ◽  
Oh Kyu Yoon ◽  
Luting Zhuo, ◽  
Ethan Grant ◽  
...  

Abstract Background Pro-inflammatory cytokines are dysregulated in Crohn’s disease (CD) and could serve as surrogate markers to improve diagnostic and therapeutic approaches, potentially addressing an unmet need. We profiled circulating biomarkers and whole blood transcriptional pathway activity to identify those associated with CD using data from the phase 2 FITZROY study with filgotinib, an oral preferential janus kinase-1 inhibitor. Methods Patients with serum and whole blood samples taken from the induction period were included. Serum cytokines were measured (ELISA), whole blood RNA sequenced, and stool samples taken to measure fecal calprotectin (FC). Spearman’s Rank correlations were assessed between biomarkers and baseline disease activity; post-treatment endoscopic improvement was measured by the Simplified Endoscopy Score for CD (SES-CD), FC and the Crohn’s Disease Activity Index. Effect of filgotinib on circulating biomarkers was also evaluated. Results Serum biomarkers (n = 168) and whole blood RNA sequencing (n = 104) were assessed. Moderate correlation between serum analytes with SES-CD and FC was noted; most highly correlated were acute phase proteins CRP (rho = 0.35 [SES-CD] and 0.47 [FC]), serum amyloid A (rho = 0.40 and 0.39, respectively) and pro-inflammatory cytokines interleukin (IL)-6 (rho = 0.31 and 0.30, respectively), IL-22 (rho = 0.36 and 0.35, respectively), and oncostatin M (rho = 0.35 and 0.33, respectively). Filgotinib treatment was associated with reduction of many candidate biomarkers, particularly in patients with treatment response. Early changes in IL-6 and IL-10 may be prognostic for endoscopic response. Conclusions Several circulating factors with potential as CD activity biomarkers were identified. Larger studies are necessary to investigate the best utility of these markers for CD.


Shock ◽  
2007 ◽  
Vol 28 (2) ◽  
pp. 148-153 ◽  
Author(s):  
Jing Lin ◽  
Yong-ming Yao ◽  
Yan Yu ◽  
Jia-ke Chai ◽  
Zhi-hong Huang ◽  
...  

2018 ◽  
Vol 24 (2) ◽  
pp. 101-111 ◽  
Author(s):  
Hans Christian D Aass ◽  
Marit Hellum ◽  
Anne-Marie Siebke Trøseid ◽  
Petter Brandtzaeg ◽  
Jens Petter Berg ◽  
...  

2018 ◽  
Vol 24 (5) ◽  
pp. 316-322 ◽  
Author(s):  
Qing He ◽  
Hua Gao ◽  
Li-ming Xu ◽  
Yan Lu ◽  
Chong Wang ◽  
...  

To overcome the lack of availability of fresh human whole blood for pyrogen detection, we explored the feasibility of utilizing cryopreserved pooled human blood to detect the responses of the pro-inflammatory cytokines IL-6 and IL-1β to LPS. Whole blood was obtained from five donors and incubated with LPS. The quantities of pro-inflammatory cytokines were measured using ELISA, and the results were compared among the samples. After the blood was cryopreserved with Dimethyl sulfoxide (DMSO) (10% v/v) and stored for 4 mo at –196℃, the detection limits of the IL-6/IL-1β responses to LPS were 0.2/0.4 endotoxin units (EU)/ml, respectively, and IL-6/IL-1β release increased in response to LPS in a dose-dependent manner. When these experiments were performed in three separate laboratories, the within-laboratory reproducibility of the IL-6/IL-1β responses was 100%/86.7%, 93.3%/100%, and 86.7%/80%, and the inter-laboratory reproducibility was 92.9%/85.7%, 64.3%/63.6%, and 57.1%/66.7%, respectively. The sensitivity (the probability of correctly classifying positive samples) and specificity (the probability of correctly classifying negative samples) of the IL-6/IL-1β tests were 81.7%/82.5% and 100%/100%, respectively. The results of this study suggest that cryopreserved pooled blood is a convenient and viable alternative for evaluating in vitro pyrogenicity. Additionally, maintaining cryopreserved pooled blood promotes safety for the user because it is released only after pretesting for infection parameters and has lower variation than fresh donations from a variety of donors.


2012 ◽  
Vol 201 (3) ◽  
pp. 327-335 ◽  
Author(s):  
Christina Bache ◽  
Ingo Spreitzer ◽  
Bjoern Becker ◽  
Bettina Loeschner ◽  
Ute Rosskopf ◽  
...  

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Jesse D Moreira ◽  
Parul Chaudhary ◽  
Kayla M Nist ◽  
Richard D Wainford

Aim: Hypothalamic paraventricular nucleus (PVN) Gαi 2 proteins mediate sympathoinhibitory responses to a high salt (HS; 4% NaCl) diet. Failure to upregulate Gαi 2 proteins in response to a HS diet results in PVN inflammation and salt sensitive hypertension (SSHTN). We hypothesize that microglial-mediated PVN inflammation precedes sympathoexcitation in Gαi 2 protein-dependent SSHTN. Methods: Three-month-old male Sprague Dawley rats implanted with ICV cannulas fitted to osmotic minipumps to centrally infuse either a control scrambled (SCR) oligodeoxynucleotide (ODN) or a Gαi 2 targeted ODN, which downregulates CNS Gαi 2 proteins by ~85%, (25μg/5μl/day/ODN) were placed on a 1-7-day normal salt (NS; 0.6% NaCl) or HS diet (n=5/group) and underwent cardiac perfusion. Brain immunohistochemistry was used to assess PVN and subfornical organ microgliosis and qualitatively assess levels of PVN pro-inflammatory cytokines (PIC) IL-1β, IL-6, and TNFα. In additional groups, MAP was assessed via radiotelemetry, and whole blood and kidneys were obtained for ELISA measurement of plasma and renal norepinephrine (NE) as estimates of sympathetic tone. Results: By 24h in control SCR ODN infused rats a HS diet, which did not alter MAP or microglial activation, evoked sympathoinhibition. In contrast, in Gαi 2 ODN infused rats a HS diet did not result in sympathoinhibition and evoked significant increases in MAP, PVN microgliosis and PVN PIC expression within 24h, and elevated renal NE content by Day 3. Conclusions: Our data suggest that in the male Sprague-Dawley model of PVN Gαi 2 protein-dependent SSHTN PVN inflammation (microgliosis and PIC production) precedes sympathoexcitation.


2003 ◽  
Vol 70 ◽  
pp. 125-133 ◽  
Author(s):  
Tim E. Cawston ◽  
Jenny M. Milner ◽  
Jon B. Catterall ◽  
Andrew D. Rowan

We have investigated proteinases that degrade cartilage collagen. We show that pro-inflammatory cytokines act synergistically with oncastatin M to promote cartilage collagen resorption by the up-regulation and activation of matrix metalloproteinases (MMPs). The precise mechanisms are not known, but involve the up-regulation of c-fos, which binds to MMP promoters at a proximal activator protein-1 (AP-1) site. This markedly up-regulates transcription and leads to higher levels of active MMP proteins.


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