scholarly journals Monocytes, Peripheral Blood Mononuclear Cells, and THP-1 Cells Exhibit Different Cytokine Expression Patterns following Stimulation with Lipopolysaccharide

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Anita Schildberger ◽  
Eva Rossmanith ◽  
Tanja Eichhorn ◽  
Katharina Strassl ◽  
Viktoria Weber
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Peripheral Blood Mononuclear Cells ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Umbilical Vein ◽  
Expression Patterns ◽  
Cytokine Release ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

THP-1 cells are widely applied to mimic monocytes in cell culture models. In this study, we compared the cytokine release from THP-1, peripheral blood mononuclear cells (PBMC), monocytes, or whole blood after stimulation with lipopolysaccharide (LPS) and investigated the consequences of different cytokine profiles on human umbilical vein endothelial cell (HUVEC) activation. WhilePseudomonas aeruginosa-stimulated (10 ng/mL) THP-1 secreted similar amounts of tumor necrosis factor alpha (TNF-α) as monocytes and PBMC, they produced lower amounts of interleukin(IL)-8 and no IL-6 and IL-10. Whole blood required a higher concentration ofPseudomonas aeruginosa(1000 ng/mL) to induce cytokine release than isolated monocytes or PBMC (10 ng/mL). HUVEC secreted more IL-6 and IL-8 after stimulation with conditioned medium derived from whole blood than from THP-1, despite equal concentrations of TNF-αin both media. Specific adsorption of TNF-αor selective cytokine adsorption from the conditioned media prior to HUVEC stimulation significantly reduced HUVEC activation. Our findings show that THP-1 differ from monocytes, PBMC, and whole blood with respect to cytokine release after stimulation with LPS. Additionally, we could demonstrate that adsorption of inflammatory mediators results in reduced endothelial activation, which supports the concept of extracorporeal mediator modulation as supportive therapy for sepsis.

scholarly journals Monitoring Tacrolimus Concentrations in Whole Blood and Peripheral Blood Mononuclear Cells: Inter- and Intra-Patient Variability in a Cohort of Pediatric Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Amedeo De Nicolò ◽  
Michele Pinon ◽  
Alice Palermiti ◽  
Antonello Nonnato ◽  
Alessandra Manca ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Pediatric Patients ◽  
Mononuclear Cells ◽  
Individual Variability ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Intracellular Concentrations ◽  
The One

Tacrolimus (TAC) is a first-choice immunosuppressant for solid organ transplantation, characterized by high potential for drug-drug interactions, significant inter- and intra-patient variability, and narrow therapeutic index. Therapeutic drug monitoring (TDM) of TAC concentrations in whole blood (WB) is capable of reducing the incidence of adverse events. Since TAC acts within lymphocytes, its monitoring in peripheral blood mononuclear cells (PBMC) may represent a valid future alternative for TDM. Nevertheless, TAC intracellular concentrations and their variability are poorly described, particularly in the pediatric context. Therefore, our aim was describing TAC concentrations in WB and PBMC and their variability in a cohort of pediatric patients undergoing constant immunosuppressive maintenance therapy, after liver transplantation. TAC intra-PBMCs quantification was performed through a validated UHPLC–MS/MS assay over a period of 2–3 months. There were 27 patients included in this study. No significant TAC changes in intracellular concentrations were observed (p = 0.710), with a median percent change of −0.1% (IQR −22.4%–+46.9%) between timings: this intra-individual variability was similar to the one in WB, −2.9% (IQR −29.4–+42.1; p = 0.902). Among different patients, TAC weight-adjusted dose and age appeared to be significant predictors of TAC concentrations in WB and PBMC. Intra-individual seasonal variation of TAC concentrations in WB, but not in PBMC, have been observed. These data show that the intra-individual variability in TAC intracellular exposure is comparable to the one observed in WB. This opens the way for further studies aiming at the identification of therapeutic ranges for TAC intra-PBMC concentrations.

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