Decreased cytokine production by mononuclear cells after severe gram-negative infections: early clinical signs and association with final outcome

Antonakos, Nikolaos; Τσαγανός, Θωμάς; Oberle, Volker; Tsangaris, Iraklis; Lada, Malvina; Pistiki, Aikaterini; Machairas, Nikolaos; Souli, María; Bauer, Michael; Giamarellos‐Bourboulis, Evangelos J.

doi:10.1186/s13054-017-1625-1

Cited by 28 publications

(20 citation statements)

References 21 publications

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“…On day 3, PBMCs were stimulated with LPS and defective levels of TNF-α were detected that persisted till day 10. Day 3 recorded the lowest levels in all three cytokines TNF, IL6, and IL8, and they remained low until day 7 compared to the prior time points, this profile was characteristic of the non-survivors' profile ( 52 ). A step toward standardization was demonstrated by Monneret et al .…”

Section: Introductionmentioning

confidence: 83%

Immune Functional Assays, From Custom to Standardized Tests for Precision Medicine

et al. 2018

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The immune response is a dynamic system that maintains the integrity of the body, and more specifically fight against infections. However, an unbalanced host immune response is highlighted in many diseases. Exacerbated responses lead to autoimmune and allergic diseases, whereas, low or inefficient responses favor opportunistic infections and viral reactivations. Conflicting situations may also occur, such as in sepsis where inflammation and compensatory immunosuppression make it difficult to deploy the appropriate drug treatment. Until the current day, assessing the immune profile of patients remains a challenge. This is especially due to the inter-individual variability—a key feature of the immune system—which hinders precise diagnosis, prognosis, and therapeutic stratification. Our incapacity to practically interpret the host response may contribute to a high morbidity and mortality, such as the annual 6 million worldwide deaths in sepsis alone. Therefore, there is a high and increasing demand to assess patient immune function in routine clinical practice, currently met by Immune Functional Assays. Immune Functional Assays (IFA) hold a plethora of potentials that include the precise diagnosis of infections, as well as prediction of secondary and latent infections. Current available products are devoted to indirect pathogen detection such as Mycobacteria tuberculosis interferon gamma release assays (IGRA). In addition, identifying the status and the underlying factors of immune dysfunction (e.g., in septic patients) may guide immune targeted therapies. Tools to monitor and stratify the immune status are currently being studied but they still have many limitations such as technical standardization, biomarkers relevance, systematic interpretation and need to be simplified, in order to set the boundaries of “healthy,” “ill,” and “critically ill” responses. Thus, the design of new tools that give a comprehensive insight into the immune functionality, at the bedside, and in a timely manner represents a leap toward immunoprofiling of patients.

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Section: Introductionmentioning

confidence: 83%

Immune Functional Assays, From Custom to Standardized Tests for Precision Medicine

et al. 2018

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“…The immunoinflammatory response in critically ill septic patients is very complex with fundamental differences in the host immune response to Gram-positive bacterial pathogens compared with Gram-negative microorganisms [ 31 – 40 ]. In our previous study [ 41 ], we also demonstrated significant difference in cytokine profile in severe Gram-positive and Gram-negative abdominal sepsis.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Mean Platelet Volume-to-Platelet Count Ratio as Biomarkers in Critically Ill and Injured Patients: Which Ratio to Choose to Predict Outcome and Nature of Bacteremia?

Djordjević

Rondović

Šurbatović

et al. 2018

Mediators of Inflammation

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Background Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume-to-platelet count (MPV/PC) ratio are readily available parameters that might have discriminative power regarding outcome. The aim of our study was to assess prognostic value of these biomarkers regarding outcome in critically ill patients with secondary sepsis and/or trauma. Methods A total of 392 critically ill and injured patients, admitted to surgical ICU, were enrolled in a prospective observational study. Leukocyte and platelet counts were recorded upon fulfilling Sepsis-3 criteria and for traumatized Injury Severity Score > 25 points. Patients were divided into four subgroups: peritonitis, pancreatitis, trauma with sepsis, and trauma without sepsis. Results NLR and MPV/PC levels were significantly higher in nonsurvivors (AUC/ROC of 0.681 and 0.592, resp., in the peritonitis subgroup; 0.717 and 0.753, resp., in the pancreatitis subgroup); MLR and PLR did not differ significantly. There was no significant difference of investigated biomarkers between survivors and nonsurvivors in trauma patients with and without sepsis except for PLR in the trauma without sepsis subgroup (significantly higher in nonsurvivors, AUC/ROC of 0.719). Independent predictor of lethal outcome was NLR in the whole cohort and in the peritonitis subgroup as well as MPV in the pancreatitis subgroup. Also, there were statistically significant differences in MPV/PC, MLR, and PLR values regarding nature of bacteremia. In general, the lowest levels had been found in patients with Gram-positive blood cultures. Conclusions NLR and MPV were very good independent predictors of lethal outcome. For the first time, we demonstrate that nature of bacteremia influences MPV/PC, MLR, and PLR. In heterogeneous cohort subgroup, analysis is essential.

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“…In a recent publication from our group we found that failure of adequate production of proinflammatory cytokines by circulating mononuclear cells 48 h after admission for sepsis was interpreted as sustaining the immunosuppression and it was associated with poor outcome. This defective production continued for at least 10 days [ 18 ]. Since CD14 dim /CD16 pos /CD45 pos cells are the monocyte subpopulation providing most of the TNFα production, the low cell count of patrolling monocytes on the third day in nonsurvivors could be associated with the immunosuppression of sepsis.…”

Section: Discussionmentioning

confidence: 99%

Increases in inflammatory and CD14dim/CD16pos/CD45pos patrolling monocytes in sepsis: correlation with final outcome

et al. 2018

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BackgroundEvidence on the changes in the absolute counts of monocyte subpopulations in sepsis is missing.MethodsFirstly, absolute counts of circulating CD14pos/HLA-DRpos/CD45pos monocytes were measured by flow cytometry in 70 patients with Gram-negative sepsis and in 10 healthy volunteers. In the second phase, immunophenotyping was performed and the absolute count of circulating inflammatory monocytes and of circulating CD14dim/CD16pos/CD45pos patrolling monocytes were measured in another 55 patients and 10 healthy volunteers. Measurements were repeated on days 3, 7, and 10. Results were correlated with survival after 28 days.ResultsGreater numbers of CD14pos/HLA-DRpos/CD45pos monocytes were found on day 1 in survivors compared to nonsurvivors (p = 0.030). Receiver operating characteristic (ROC) analysis showed that a cutoff higher than 337 cells/mm3 on day 1 could discriminate between survivors and nonsurvivors with a positive predictive value (PPV) of 91.1%. Logistic regression including Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE) II score showed that an absolute count greater than 337 cells/mm3 was independently associated with unfavorable outcome (odds ratio (OR) 0.19, p = 0.050). The absolute counts of inflammatory and of CD14dim/CD16pos/CD45pos monocytes were greater in patients than healthy controls during the entire 10 days of follow-up. The absolute counts on day 3 of CD14dim/CD16pos/CD45pos monocytes were greater in survivors than nonsurvivors (p = 0.027). ROC analysis revealed that the cutoff at 27 cells/mm3 could discriminate between survivors and nonsurvivors with PPV of 94.1%. Logistic regression including age, SOFA score, and APACHE II score showed that an absolute count greater than 27 cells/mm3 was independently associated with unfavorable outcome (OR 0.06, p = 0.033). Logistic regression analysis showed that intra-abdominal infection on day 1 was predictive of low CD14dim/ CD16pos/CD45pos count on day 3.ConclusionCirculating counts of inflammatory and patrolling monocytes are greatly increased in Gram-negative sepsis. Absolute counts of CD14pos/HLA-DRpos/CD45pos monocytes on day 1 and CD14dim/CD16pos/CD45pos monocytes on day 3 are independently associated with final outcome.Trial registrationClinicalTrials.gov, NCT01223690. Registered retrospectively on 18 October 2010.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-1977-1) contains supplementary material, which is available to authorized users.

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Decreased cytokine production by mononuclear cells after severe gram-negative infections: early clinical signs and association with final outcome

Cited by 28 publications

References 21 publications

Immune Functional Assays, From Custom to Standardized Tests for Precision Medicine

Immune Functional Assays, From Custom to Standardized Tests for Precision Medicine

Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Mean Platelet Volume-to-Platelet Count Ratio as Biomarkers in Critically Ill and Injured Patients: Which Ratio to Choose to Predict Outcome and Nature of Bacteremia?

Increases in inflammatory and CD14dim/CD16pos/CD45pos patrolling monocytes in sepsis: correlation with final outcome

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