scholarly journals Boosted Pro-Inflammatory Activity in Human PBMCs by Lipopolysaccharide and SARS-CoV-2 Spike Protein Is Regulated by α-1 Antitrypsin

2021 ◽  
Vol 22 (15) ◽  
pp. 7941
Author(s):  
Srinu Tumpara ◽  
Anna R. Gründing ◽  
Kokilavani Sivaraman ◽  
Sabine Wrenger ◽  
Beata Olejnicka ◽  
...  
Keyword(s):  
Human Plasma ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Statistical Significance ◽  
Spike Protein ◽  
Human Pbmcs ◽  
Experimental Conditions ◽  
Peripheral Blood Mononuclear ◽  
Anti Inflammatory

For the treatment of severe COVID-19, supplementation with human plasma-purified α-1 antitrypsin (AAT) to patients is currently considered. AAT inhibits host proteases that facilitate viral entry and possesses broad anti-inflammatory and immunomodulatory activities. Researchers have demonstrated that an interaction between SARS-CoV-2 spike protein (S) and lipopolysaccharides (LPS) enhances pro-inflammatory responses in vitro and in vivo. Hence, we wanted to understand the potential anti-inflammatory activities of plasma-derived and recombinant AAT (recAAT) in a model of human total peripheral blood mononuclear cells (PBMCs) exposed to a combination of CHO expressed trimeric spike protein and LPS, ex vivo. We confirmed that cytokine production was enhanced in PBMCs within six hours when low levels of LPS were combined with purified spike proteins (“spike”). In the presence of 0.5 mg/mL recAAT, however, LPS/spike-induced TNF-α and IL-1β mRNA expression and protein release were significantly inhibited (by about 46–50%) relative to LPS/spike alone. Although without statistical significance, recAAT also reduced production of IL-6 and IL-8. Notably, under the same experimental conditions, the plasma-derived AAT preparation Respreeza (used in native and oxidized forms) did not show significant effects. Our findings imply that an early pro-inflammatory activation of human PBMCs is better controlled by the recombinant version of AAT than the human plasma-derived AAT used here. Considering the increasing clinical interest in AAT therapy as useful to ameliorate the hyper-inflammation seen during COVID-19 infection, different AAT preparations require careful evaluation.

scholarly journals Integrated cytokine and metabolite analysis reveals immunometabolic reprogramming in COVID-19 patients with therapeutic implications

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nan Xiao ◽  
Meng Nie ◽  
Huanhuan Pang ◽  
Bohong Wang ◽  
Jieli Hu ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Rhesus Macaques ◽  
Fatal Outcome ◽  
Organ Injury ◽  
Cytokine Release ◽  
Serum Samples ◽  
Peripheral Blood Mononuclear

AbstractCytokine release syndrome (CRS) is a major cause of the multi-organ injury and fatal outcome induced by SARS-CoV-2 infection in severe COVID-19 patients. Metabolism can modulate the immune responses against infectious diseases, yet our understanding remains limited on how host metabolism correlates with inflammatory responses and affects cytokine release in COVID-19 patients. Here we perform both metabolomics and cytokine/chemokine profiling on serum samples from healthy controls, mild and severe COVID-19 patients, and delineate their global metabolic and immune response landscape. Correlation analyses show tight associations between metabolites and proinflammatory cytokines/chemokines, such as IL-6, M-CSF, IL-1α, IL-1β, and imply a potential regulatory crosstalk between arginine, tryptophan, purine metabolism and hyperinflammation. Importantly, we also demonstrate that targeting metabolism markedly modulates the proinflammatory cytokines release by peripheral blood mononuclear cells isolated from SARS-CoV-2-infected rhesus macaques ex vivo, hinting that exploiting metabolic alterations may be a potential strategy for treating fatal CRS in COVID-19.

Novel Concentration-Dependent Roles for Heparin in Modifying LPS-Induced Activation of Mononuclear Cells in Whole Blood.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 927-927
Author(s):  
Helene Hochart ◽  
Vince Jenkins ◽  
Owen P. Smith ◽  
Barry White ◽  
James O’Donnell
Keyword(s):  
Whole Blood ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Anticoagulant Activity ◽  
Serum Free ◽  
Anti Inflammatory ◽  
Serum Free Conditions ◽  
Dose Dependent ◽  
Stimulation Of

Abstract Background: In addition to their etsblished anticoagulant activity, unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are known to possess clinically important immuno-modulatory properties. However different studies have reported conflicting pro- and anti-inflammatory effects in association with heparin. Moreover, the molecular basis for these heparin effects on inflammation remains unclear. In view of the wide and diverse clinical indications for heparin, it is clearly of direct translational relevance to define how UFH and LMWH differentially regulate inflammatory responses to LPS in-vivo. Objectives: To determine how UFH and LMWH regulate lipopolysaccharide (LPS)-induced activation of human mononuclear cells in whole blood, and define the role of lipopolysaccharide binding protein (LBP) in mediating this effect. Methods: Whole blood was pre-treated with UFH or LMWH (0.1–200 IU/ml), prior to stimulation with LPS (10ng/ml). After 6 hours, monocyte pro-inflammatory cytokine (interleukin (IL)-1b, IL-6, IL-8, and TNF-a) secretion was determined by plasma ELISA. Parallel experiments using THP-1 cell line and primary monocytes were performed under serum-free conditions, in the presence or absence of varying doses of recombinant human LBP (range: 50–100nM). Results: Under serum-free conditions, heparin demonstrated dose-dependent anti -inflammatory effects, significantly reducing secretion of pro-inflammatory cytokines (IL-1b, IL-6, IL-8, and TNF-a) in response to LPS-stimulation of THP-1 cells and primary monocytes. In contrast, in the presence of LBP, both UFH and LMWH demonstrated dose-dependent pro-inflammatory effects at all heparin concentrations. In ex-vivo whole blood experiments, pro-inflammatory effects (increased IL-1b and IL-8 following LPS-stimulation) of heparin were also observed, but only at supra-therapeutic doses (10–200IU/ml). Conclusion: In keeping with previous reports, we have demonstrated that both UFH and LMWH can significantly down-regulate cytokine (TNF-a, IL-1b, IL-6 and IL-8) secretion in response to LPS-activation in-vitro. However our novel data demonstrate that the effect of heparin on monocyte activation by LPS is significantly more complex in the setting of whole blood. Firstly, in contrast to the anti-inflammatory effects observed under serum-free conditions, we found that in whole blood, high concentrations of heparin exerted marked pro-inflammatory effects. Secondly we have also demonstrated that the effects of heparin in whole blood are entirely dependent upon heparin concentration and LBP concentration.

scholarly journals Protective Effect of Silibinin on Lipopolysaccharide-Induced Inflammatory Responses in Equine Peripheral Blood Mononuclear Cells, an In Vitro Study

Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2022
Author(s):  
Enrico Gugliandolo ◽  
Rosalia Crupi ◽  
Vito Biondi ◽  
Patrizia Licata ◽  
Salvatore Cuzzocrea ◽  
...  
Keyword(s):  
Protective Effect ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Mammalian Species ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Anti Inflammatory

Although inflammation is an important physiological response, it plays a prominent role in several diseases across the mammalian species. In horses, in particular, inflammation secondary to bacterial infection or translocation is one of the most frequent causes of morbidity and mortality. Research in new molecules with anti-inflammatory and immunomodulatory proprieties and safe use profile is constantly an active field; natural compounds are an important source of molecules with peculiar properties such as antioxidants, anti-inflammatory and immune modulating. Silibinin, a natural polyphenolic flavonoid, extracted from plant milk thistle, Silybum marianum, has been reported to have actions such as antioxidant immunomodulatory and anti-inflammatory. The aim of this study was to test the effect of silibinin on lipopolysaccharide (LPS)-induced inflammatory response in equine peripheral blood mononuclear cells (PBMCs). Our results showed the protective effect of silibinin 10 μM and 50 μM in equine PBMCs stimulated with LPS. Silibilinin was able to prevent the LPS induced increased levels of TNF-α, IL-1β, IL-6 and IL-8. The results from this study on LPS-stimulated equine PBMCs showed that silibinin could be a useful pharmacological approach in treatment or prevention of several inflammatory conditions in horse.

Differential effects of platelets and platelet inhibition by ticagrelor on TLR2- and TLR4-mediated inflammatory responses

2015 ◽  
Vol 113 (05) ◽  
pp. 1035-1045 ◽  
Author(s):  
Andre J. van der Ven ◽  
Niels Riksen ◽  
Gerard Rongen ◽  
Sabine Tacke ◽  
T. N. A. van den Berg ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Platelet Inhibition ◽  
P2y12 Receptor ◽  
Oral Dosage ◽  
Induced Response ◽  
Double Blind ◽  
Peripheral Blood Mononuclear ◽  
Cytokine Responses ◽  
Anti Inflammatory

SummaryPlatelets and platelet-monocyte interaction play an important role in inflammation. Both pro- and anti-inflammatory effects of platelet inhibition have been reported in animal models. This study aimed to investigate the effect of platelets and platelet inhibition by the new P2Y12 receptor antagonist ticagrelor on monocyte function, as assessed by cytokine responses to Toll-like Receptor (TLR) ligands. In a set of in vitro experiments, peripheral blood mononuclear cells (PBMC) incubated with the TLR2 ligand Pam3CSK4 produced less cytokines in the presence of platelets, whereas platelets increased the production of cytokines when PBMC were exposed to TLR4 ligand lipopolysaccharide (LPS). These effects of platelets were dependent on direct platelet-leukocyte aggregation and for the Pam3CSK4-induced response, on phagocytosis of platelets by monocytes. In a double blind, placebo-controlled crossover trial in healthy volunteers, a single oral dosage of 180 mg ticagrelor reduced platelet-monocyte complex (PMC) formation. This was associated with an increase in pro-inflammatory cytokines in blood exposed to Pam3CSK4, but a decrease in these cytokines in blood exposed to LPS. These findings show that platelets differentially modulate TLR2- and TLR4-mediated cytokine responses of PBMC. Through inhibition of platelet-leukocyte interaction, P2Y12 receptor antagonists may either exert a pro- or anti-inflammatory effect during infections depending on the TLR primarily involved.

scholarly journals Ex vivo peripheral blood mononuclear cell response to R848 in children after supplementation with the probiotic Lactobacillus acidophilus NCFM/Bifidobacterium lactis Bi-07

2021 ◽  
Vol 12 (1) ◽  
pp. 85-93
Author(s):  
G.P. DeMuri ◽  
L.M. Lehtoranta ◽  
J.C. Eickhoff ◽  
M.J. Lehtinen ◽  
E.R. Wald
Keyword(s):  
Lactobacillus Acidophilus ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Open Label ◽  
Peripheral Blood Mononuclear ◽  
Upper Respiratory Infection ◽  
Beneficial Effects ◽  
Inflammatory Protein ◽  
Anti Inflammatory

Several studies have demonstrated a decrease in upper respiratory infection (URI) frequency and severity in subjects taking probiotic supplements. We hypothesised beneficial effects of probiotics on viral URI in children are due to modulation of inflammatory innate immune responses. We tested this hypothesis, providing children with a probiotic combination of Lactobacillus acidophilus/Bidfidobacterium animalis ssp. lactis Bi-07 (NCFM/Bi-07) and measuring levels of cytokines in response to stimulation of peripheral blood mononuclear cells (PBMCs) to toll-like receptor (TLR) 7/8 agonist resiquimod (R848). In this open label study, 21 (2 dropouts) children received probiotic containing 5×109 cfu each of NCFM/(Bi-07) daily for 30 days. Whole blood was taken from each subject at study entry and 30 days for culture of PBMCs. PBMCs stimulated with resiquimod (R848) or unstimulated were incubated and a panel of immune markers was measured. There was a significant decrease in the net (stimulated-null) level of myeloid progenitor inhibitory factor 1 (MPIF-1) (mean decrease 0.1 ng/ml, 95% confidence interval 0.01-0.24, P=0.032) following probiotic supplementation. The change in immune marker levels after supplementation, when analysed together with respect to expected inflammatory/anti-inflammatory effects, was increased for interleukin (IL)-10 and decreased for MPIF-1, IL-8, interferon gamma induced protein 10, macrophage inflammatory protein 3 alpha (MIP-3α) and E-selectin (P=0.01). Adverse events were mild. In conclusion, supplementation with this probiotic combination was safe and resulted in significant modulation of PBMC limited immune response to TLR7/8 agonist R848 and in levels of MPIF-1 and MIP-3α. The anti-inflammatory effect may be one mechanism by which probiotics modulate the immune system however further study is needed.

AB0110 ADIPONECTIN INDUCES PRO-INFLAMMATORY CHEMOKINE AND CYTOKINE PRODUCTION BY PERIPHERAL BLOOD MONONUCLEAR CELLS AND FIBROBLAST-LIKE SYNOVIOCYTES FROM NON-INFLAMED SUBJECTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1355-1356
Author(s):  
Y. Zhang ◽  
J. Aldridge ◽  
G. K. Vasileiadis ◽  
A. C. Lundell ◽  
A. Rudin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Multiplex Assay ◽  
Human Pbmcs ◽  
Peripheral Blood Mononuclear ◽  
Preclinical Phase ◽  
Blood Mononuclear Cells ◽  
Fibroblast Like Synoviocytes

Background:Adiponectin is a cytokine mainly secreted by the adipose tissue1, whose circulating levels are paradoxically low in subjects with obesity and associate with a beneficial metabolic profile2., Recent studies have shown that adiponectin levels are elevated in both serum and synovial fluid collected from patients with rheumatoid arthritis (RA)3,4. Moreover, adiponectin is able to induce the production of interleukin (IL)-6, tumor necrosis factor (TNF), CXCL1 and CXCL8 by lymphocytes from healthy subjects5, and of IL-6 and CXCL8 by fibroblast-like synoviocytes (FLS) from patients with RA6. However, it is not clear if adiponectin is able to initiate the inflammatory processes associated with the preclinical phase of RA.Objectives:We aim to determine if adiponectin is able to induce inflammatory responses in peripheral blood mononuclear cells (PBMCs) and FLS from non-inflamed subjects.Methods:Human PBMCs were collected from healthy donors, whereas non-inflamed FLS from non-arthritic patients who underwent diagnostic arthroscopy due to previous trauma. PBMCs (1× 105cells/well in 96-well plate) and FLS (5000 cells/well in 96-well plate) were stimulated using 5 μg/ml recombinant human total adiponectin protein, and the supernatants were collected 48 hours after stimulation. Phytohemagglutinin (PHA) and TNF were used as positive controls to activate PBMCs and FLS, respectively. Using multiplex assay and ELISA, we screened the production of 13 chemokines and 12 cytokines from healthy human PBMCs and non-inflamed FLS.Results:Adiponectin was able to stimulate a distinct profile of chemokines and cytokines in PBMCs and FLS. In both healthy PBMCs and non-inflamed FLS adiponectin induced the production of CXCL1, CXCL5, CXCL8, CCL2 and IL-6. Moreover, CCL3, CCL20, CCL4, CCL17, TNF, IL-10 and GM-CSF were induced by adiponectin only in healthy PBMCs, whereas CXCL10, CCL5 and CCL11 only in non-inflamed FLS (Fig. 1 and 2).Figure 1.Adiponectin induces the production of various chemokines from PBMCs (A) and FLS (B). CXCL8 (#) was measured using ELISA, and other chemokines were measured using multiplex assay. The fold change of CXCL1 in FLS (†) was not calculated because its level before stimulation was undetectable.Conclusion:We here report that adiponectin has pro-inflammatory properties as it induced chemokine and cytokine production from human healthy PBMCs and non-inflamed FLS. As adiponectin is able to induce pro-inflammatory responses from non-inflamed cells, we suggest that this adipokine might be implicated in the preclinical phase of RA pathogenesis.References:[1]Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm 2013;2013:139239.[2]Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract 2014;105:141-50.[3]Otero M, Lago R, Gomez R, et al. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis 2006;65:1198-201.[4]Schaffler A, Ehling A, Neumann E, et al. Adipocytokines in synovial fluid. JAMA 2003;290:1709-10.[5]Frommer KW, Zimmermann B, Meier FM, et al. Adiponectin-mediated changes in effector cells involved in the pathophysiology of rheumatoid arthritis. Arthritis Rheum 2010;62:2886-99.[6]Kitahara K, Kusunoki N, Kakiuchi T, Suguro T, Kawai S. Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts. Biochem Biophys Res Commun 2009;378:218-23.Figure 2.Adiponectin induces the production of IL-6 PBMCs (A) FLS (B) measured using ELISA.Disclosure of Interests:Yuan Zhang: None declared, Jonathan Aldridge: None declared, Georgios K. Vasileiadis: None declared, Anna-Carin Lundell: None declared, Anna Rudin Consultant of: Astra/Zeneca, Cristina Maglio: None declared

NCS 613 exhibits anti-inflammatory effects on PBMCs from lupus patients by inhibiting p38 MAPK and NF-κB signalling pathways while reducing proinflammatory cytokine production

2013 ◽  
Vol 91 (5) ◽  
pp. 353-361 ◽  
Author(s):  
Issaka Yougbaré ◽  
Gilles Boire ◽  
Michelle Roy ◽  
Claire Lugnier ◽  
Éric Rouseau
Keyword(s):  
P38 Mapk ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Pde4 Inhibitor ◽  
Human Pbmcs ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Tnf Α ◽  
Anti Inflammatory

Systemic lupus erythematosus (SLE) is a polymorphic and multigenic autoimmune disease that evolves into progressive and chronic inflammation of multiple joints and organs. Phosphorylation and activation of p38 MAPK, along with the resulting overproduction of interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α is a hallmark of inflammatory disorders. Here, we investigated the anti-inflammatory pathway modulated by NCS 613, a specific PDE4 inhibitor, on human peripheral blood mononuclear cells (PBMCs) from 5 healthy donors and 12 SLE patients. PDE4 subtypes, p38 MAPK, and IκBα protein levels were analyzed by Western blot, while NF-κB and PDE4B immunostaining was assessed in control and lipopolysaccharide (LPS) -pretreated PBMCs. Proinflammatory cytokines were quantified by ELISA, while IL-1β mRNA was resolved by RT–qPCR. NCS 613 treatment decreased PDE4B and upregulated PDE4C in human PBMCs from healthy donors and SLE patients. LPS stimulation increased p38 MAPK phosphorylation and NF-κB translocation to the nucleus, which was abolished by NCS 613 treatment. Concomitantly, NCS 613 restored IκBα detection levels in human PBMCs from both healthy donors and SLE patients. This compound also abolished LPS-induced inflammation in PBMCs by reducing IL-6, IL-8, and TNF-α cytokines. NCS 613 is a small molecule displaying anti-inflammatory properties that may provide an alternative or complementary strategy for SLE management.

scholarly journals Ostertagia ostertagi Mediates Early Host Immune Responses via Macrophage and Toll-Like Receptor Pathways

2021 ◽  
Vol 89 (6) ◽  
Author(s):  
Mariam Bakshi ◽  
Deborah Hebert ◽  
Connor Gulbronson ◽  
Gary Bauchan ◽  
Wenbin Tuo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Time Course ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Ostertagia Ostertagi ◽  
Host Immune Responses ◽  
Tnf Α ◽  
Anti Inflammatory

ABSTRACT Ostertagia ostertagi is an abomasal parasite with significant economic impact on the cattle industry. Early host immune responses are poorly understood. Here, we examined time course expression of Toll-like receptors (TLRs) in peripheral blood mononuclear cells (PBMC) during infection where PBMC macrophages (Mϕ) generated both pro- and anti-inflammatory responses when incubated with excretory/secretory products (ESP) from fourth-stage larvae (OoESP-L4) or adult worms (OoESP-Ad). First, changes in cell morphology clearly showed that both OoESP-L4 and OoESP-Ad activated PBMC-Mϕ in vitro, resulting in suppressed CD40 and increased CD80 expression. Expression of mRNAs for TLR1, -4, -5, and -7 peaked 7 days postinfection (dpi) (early L4), decreased by 19 dpi (postemergent L4 and adults) and then increased at 27 dpi (late adults). The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) (transcript and protein) increased in the presence of OoESP-Ad, and the anti-inflammatory cytokine interleukin 10 (IL-10) (protein) decreased in the presence of OoESP-L4 or OoESP-Ad; however, IL-10 mRNA was upregulated, and IL-6 (protein) was downregulated by OoESP-L4. When PBMC-Mϕ were treated with ligands for TLR4 or TLR5 in combination with OoESP-Ad, the transcripts for TNF-α, IL-1, IL-6, and IL-10 were significantly downregulated relative to treatment with TLR4 and TLR5 ligands only. However, the effects of TLR2 ligand and OoESP-Ad were additive, but only at the lower concentration. We propose that O. ostertagi L4 and adult worms utilize competing strategies via TLRs and Mϕ to confuse the immune system, which allows the worm to evade the host innate responses.

scholarly journals Exercise reduced pentraxin 3 levels produced by endotoxin-stimulated human peripheral blood mononuclear cells in obese individuals

2017 ◽  
Vol 242 (12) ◽  
pp. 1279-1286 ◽  
Author(s):  
Aaron L Slusher ◽  
Yoshimi Shibata ◽  
Michael Whitehurst ◽  
Arun Maharaj ◽  
Justin M Quiles ◽  
...  
Keyword(s):  
Aerobic Exercise ◽  
Peripheral Blood Mononuclear Cells ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Normal Weight ◽  
Pentraxin 3 ◽  
Peripheral Blood Mononuclear ◽  
Inflammatory Protein ◽  
Blood Mononuclear Cells ◽  
Anti Inflammatory

The purpose of this study was to determine whether obesity would reduce the capacity of peripheral blood mononuclear cells (PBMCs) to produce the anti-inflammatory protein pentraxin 3 (PTX3) in response to ex vivo stimulation with lipopolysaccharide (LPS), and if acute aerobic exercise would enhance this PTX3 production capacity. In addition, the inter-relationships of LPS-induced PTX3 with the inflammatory cytokines (interleukin 6 [IL-6], IL-10, and tumor necrosis factor alpha) were examined. Twenty-one healthy subjects (10 obese and 11 normal-weight) performed an acute bout of aerobic exercise at 75% VO2max. The capacity of PBMCs to produce PTX3 ex vivo following LPS stimulation was the same in obese and normal-weight subjects at rest, and decreased equally in both subject groups following acute aerobic exercise. This is in contrast to plasma PTX3, which is lower in obese subjects at rest and increased equally in both obese and normal-weight subjects following exercise. In addition, ex vivo PTX3 production was positively associated with IL-6 and IL-10 in response to acute aerobic exercise ( r = 0.686, P = 0.020; r = 0.744, P = 0.009, respectively) in normal-weight, but not in obese individuals ( r = 0.429, P = 0.249; r = 0.453, P = 0.189, respectively). These findings indicate that concentrations of PTX3 observed in plasma are relatively independent of those produced by PBMCs ex vivo and the mechanisms associated with PTX3-mediated anti-inflammatory signaling may differ during obesity. Impact statement Our laboratory has previously demonstrated that obese individuals present with lower plasma concentrations of the anti-inflammatory protein pentraxin 3 (PTX3), whereas acute aerobic exercise increases plasma PTX3 levels similarly compared to normal-weight individuals. As a follow-up, the present study demonstrates that PBMCs isolated from obese and normal-weight individuals produce comparable amounts of PTX3 ex vivo in response to lipopolysaccharide (LPS). Furthermore, given that acute aerobic exercise reduced the ex vivo production of PTX3 in both groups, our results clearly indicate that plasma PTX3 levels are relatively independent of those produced by PBMCs ex vivo. In addition, our findings suggest that the mechanisms associated with PTX3-mediated production of the anti-inflammatory cytokine interleukin 10 may be impaired in obese individuals, and thus provides a key finding necessary for the elucidation of PTX3’s role in the mediation of anti-inflammatory profiles and the subsequent amelioration of inflammatory disease during obesity.

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