Baseline Levels and Temporal Stability of 27 Multiplexed Serum Cytokine Concentrations in Healthy Subjects

INTROduCTION Chemokines are cytokines with chemotactic functions in the initiation and maintenance of immune reactions. They have also been shown to regulate other processes such as cancer progression and cancer cell migration.ObjECTIvEs The aim of this study was to determine the prognostic role of serum levels of chemokine (C-C motif) ligand 2 (CCL2) and chemokine (C-C motif) ligand 5 (CCL5) in patients with colorectal cancer. PATIENTs ANd METhOdsThe study included a group of 45 patients with colorectal cancer. The serum concentrations of CCL2 and CCL5 were measured preoperatively. Peripheral blood mononuclear cells (PBMC) from patients' blood were isolated and cultured alone or with cancer cells. The concentrations of chemokines in serum and culture supernatants were measured using the cytometric bead array method. The cut-off points for serum chemokine levels were set based on the receiver-operating characteristic curve analysis at a level of 103.6 pg/ml for CCL2 and of 11933.2 pg/ml for CCL5. The survival analysis and multivariate analysis of prognostic factors were performed. REsuLTsThe 5-year survival was 57.5% for the group with low CCL2 levels and 23.87% for the group with high CCL2 levels. For the groups with low and high CCL5 levels, the survival was 18.3% and 49.3%, respectively. For CCL2, the survival of the low-level group was significantly better than that of the highlevel group (P = 0.0028). In the Cox proportional hazard model, radicality of resection (P = 0.001) and CCL2 levels (P = 0.029) were independent prognostic factors.CONCLusIONs The serum level of CCL2 in patients with colorectal cancer may have prognostic value. One of the possible mechanisms of CCL2 production is the interaction of PBMC with cancer cells.

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“…For CCL5, the respective levels were from 10 264.21 pg/ml to 11 740.25 pg/ml. 40 These levels are coherent with our results.…”

Section: -38supporting

confidence: 92%

Preoperative serum chemokine (C-C motif) ligand 2 levels and prognosis in colorectal cancer

Szczepanik¹,

Siedlar²,

Szura³

et al. 2015

Polish Archives of Internal Medicine

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“…For some assays, the proteins could not be detected in more than 60% of the tested sera (Table 2). Indeed, both platforms failed to robustly detect the GM-CSF, IL-1β, IL-2 and IL-5 cytokines for which previous investigations had reported significant variations in expression either during MDE treatment or at baseline in comparison to healthy controls (Biancotto et al, 2013;Dahl et al, 2014;Hernandez et al, 2008;Schmidt et al, 2014;Shelton et al, 2015). These types of inconsistency in the results have already been reported (Breen et al, 2011;Chaturvedi et al, 2011;Dabitao et al, 2011;Dupuy et al, 2013;Fu et al, 2010).…”

Section: Discussionmentioning

confidence: 89%

“…In biological human fluids, the seasonal, hormonal, and circadian physiological variability in the circulating concentrations of cytokines/chemokines/growth factors remains poorly investigated both in psychiatric patients as a function of their treatments as well as in healthy subjects. Furthermore, large differences exist among individuals (Agorastos et al, 2014;Biancotto et al, 2013;Mueller et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

How to: Measuring blood cytokines in biological psychiatry using commercially available multiplex immunoassays

Belzeaux

Lefebvre

Lazzari

et al. 2017

Psychoneuroendocrinology

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Cytokines produced by both immune and non-immune cells are likely to play roles in the development and/or progression of psychiatric disorders. Indeed, many investigators have compared the blood cytokine levels in psychiatric patients with those of healthy controls or monitored their levels in patients during disease progression to identify biomarkers. Nevertheless, very few studies have confirmed that such cytokines remain stable in healthy individuals through periods of weeks and months. This is an important issue to consider before using blood cytokine levels as biomarkers of disease traits, disease state, or treatment response. Although multiplex assay technology represents an advance in identifying biomarkers because it allows simultaneous examination of large panels of analytes from a small volume of sample, it is necessary to verify whether these assays yield enough sensitivity and reproducibility when applied to the blood from neuropsychiatric patients. Therefore, we compared two multiplex immunoassays, the bead-based Luminex® (Bio-Rad) and the electro-chemiluminescence-based V-plex® (MesoScaleDiscovery), for the detection and quantification of 31 cytokines, chemokines and growth factors in both the sera and plasma of patients with major depressive episodes (MDE) and age-and sex-matched healthy control subjects during a 30-week period. Although both platforms exhibited low coefficients of variability (CV) between the duplicates in the calibration curves, the linearity was better in general for the V-PLEX® platform. However, neither platform was able to detect the absolute values for all of the tested analytes. Among the 16 analytes that were detected by both assays, the intra-assay reproducibility was in general better with the V-PLEX® platform. Although it is not a general rule that the results from sera and plasma will be correlated, consistent results were more frequent with the V-PLEX® platform. Furthermore, the V-PLEX® results were more consistent with the gold standard ELISA simplex assay for IL-6 in both sera and plasma. The intra-individual variability of the measurements, among the sera and plasma for the 4 samples harvested from each healthy individual, was low for Eotaxin, G-CSF, IL-4, IL-7, IL-9, IL-12p40, IL-12p70, IL-15, MIP-1β, PDGF-BB, TNF, TNF-β and VEGF, but intermediate or high for IFN-γ, IL-6, IL-8, IL-10, and IP10. Together, these data suggest that extreme caution is needed in translating the results of multiplex cytokine profiling into biomarker discovery in psychiatry. Dear Editor,We thank you and the Editor in chief, Robert Dantzer, for reaching the conclusion to ultimately publish our manuscript. Following your suggestion, we changed the tiltle to: "How to: Measuring blood cytokines in biological psychiatry using commercially available multiplex immunoassays".We were concerned by the persistent negative comments of Reviewer#3, stressing out that our comparison between the two platforms we have worked with suffers a number of theoretical and technical limitations because...

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“…On the other hand, G-CSF, IL-12 and IL-17A levels were lower in patients with HCC compared to those in healthy adults. For other cytokines, previous studies showed the inconsistent results [31,32]. Therefore future study with healthy control, chronic hepatitis or liver cirrhosis will give more information about cytokine roles in patients with HCC.…”

Section: Discussionmentioning

confidence: 96%

Interleukin-8 level as a prognostic marker in patients with hepatitis B virus-associated hepatocellular carcinoma treated with transarterial chemoembolization

et al. 2015

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Baseline Levels and Temporal Stability of 27 Multiplexed Serum Cytokine Concentrations in Healthy Subjects

Cited by 94 publications

References 20 publications

Preoperative serum chemokine (C-C motif) ligand 2 levels and prognosis in colorectal cancer

Preoperative serum chemokine (C-C motif) ligand 2 levels and prognosis in colorectal cancer

How to: Measuring blood cytokines in biological psychiatry using commercially available multiplex immunoassays

Interleukin-8 level as a prognostic marker in patients with hepatitis B virus-associated hepatocellular carcinoma treated with transarterial chemoembolization

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