Individual Inflammatory Markers Research Articles

Associations between inflammatory burden index, prostate cancer, and mortality among middle-aged and elderly individuals.

Inflammation plays a crucial role in prostate cancer (PCa) progression and mortality. This study aimed to investigate the predictive value of the inflammatory burden index (IBI) and its components for mortality risk among men aged 40 years and older. A total of 7,344 participants from the NHANES 2001-2010 were included. High PCa risk was defined as a %fPSA greater than 25% and a tPSA level less than 4.0 ng/mL. Cox regression and logistic regression analyses were conducted to assess the association between IBI, PCa risk, and mortality. Receiver operating characteristic (ROC) curve analysis and random survival forest (RSF) model were utilized to evaluate the predictive value of IBI and its components for mortality. Elevated IBI levels were significantly associated with an increased risk of all-cause mortality (HR = 1.08 [1.05-1.10]) and cancer mortality (HR = 1.11 [1.07-1.15]). High-risk PCa cases also exhibited elevated mortality risk (all-cause: HR = 1.35 [1.19-1.54]; cancer: HR = 1.65 [1.27-2.14]). Additionally, the combined effect of elevated IBI levels and high PCa risk showed a synergistic impact on mortality outcomes (all-cause: HR = 1.49 [1.27-1.74]; cancer: HR = 1.76 [1.29-2.40]). ROC curve analysis revealed that IBI had the highest AUC for predicting all-cause mortality (AUC = 0.690 at 3 years, 0.622 at 5 years, 0.634 at 10 years, and 0.632 at 15 years) compared to its individual components (CRP, NEU, LYM). RSF analysis highlighted IBI as the most significant predictor of all-cause and cancer mortality. The combined effect of elevated IBI levels and high PCa risk demonstrated a synergistic impact on increased mortality risk among men aged 40 years and older. IBI demonstrated superior predictive performance for mortality outcomes compared to individual inflammatory markers. These findings underscore the potential utility of IBI as a prognostic biomarker for mortality risk assessment in individual with high PCa risk.

Unveiling the Roles of Immune Function and Inflammation in the Associations Between Dietary Patterns and Incident Type 2 Diabetes

Objective To investigate the associations between data-driven dietary patterns, immune function, and incident type 2 diabetes (T2D) and the mediating effects of immune function. Methods This study included 375,665 participants without diabetes at baseline in the UK Biobank study. Dietary patterns were derived through principal component analysis of food frequency questionnaire data. Immune function was assessed using 14 individual inflammatory markers and an integrated low-grade inflammation score (INFLA-score). Cox proportional hazard models were used to estimate the associations of dietary patterns or immune function with incident T2D. Linear regressions were used to estimate the associations of dietary patterns with immune function. Mediating effects of immune function were quantified. Results During a median 14.6-year follow-up, 13,932 participants developed T2D. Four dietary patterns were identified: prudent diet (high in whole grains, vegetables, fruits, fish), wheat/dairy/eggs restrictive diet (limiting these foods), meat-based diet (high in red/processed meat, salt), and full-cream dairy diet (preference for full cream milk or dairy products). The prudent diet was negatively (HRQ4 vs Q1, 0.69 [95% CI, 0.65–0.72]), while the wheat/dairy/eggs restrictive diet (HRQ4 vs Q1, 1.08 [95% CI, 1.03–1.13]), meat-based diet (HRQ4 vs Q1, 1.12 [95% CI, 1.06–1.17]), and full-cream dairy diet (HRQ4 vs Q1, 1.08 [95% CI, 1.03–1.12]) were positively associated with incident T2D (all p for trend ≤0.04). The prudent diet was negatively and the full-cream dairy diet was positively associated with most inflammatory markers. Most inflammatory markers, especially INFLA-score (HR, 1.18 [95% CI, 1.16–1.20]), were positively associated with incident T2D. INFLA-score mediated 13% of the association with incident T2D for the prudent diet and 34% for the full-cream dairy diet. Conclusions This study identified four distinct dietary patterns and a range of inflammatory markers associated with incident T2D. A notable proportion of the associations between dietary patterns and T2D was mediated by immune function.

The Role of Inflammatory Markers for Diagnostics and Optimization of Therapy in Psychiatry

Background: the results of studying the role of neuroinflammation in the pathogenesis of chronic mental disorders guide the scientific search for ways to apply conceptual notions to clinical practice. The aim: to present an overview of clinical and biological studies conducted jointly by clinicians and employees of the Laboratory of Neuroimmunology of the FSBSI “Mental Health Research Centre” and aimed at determination of the significance of immune biomarkers for the diagnosis, prognosis and treatment of various types of mental pathology. Method: the methodological equipment of this study is provided by the use of the original “Neuro-immuno-test” medical technology, developed at the FSBSI “Mental Health Researh Centre”, in comparison with the clinical data. Results and discussion: summarizing the results of many years of research showed that various inflammatory markers, determined in the blood of patients, can be used to assess the level of inflammation in the brain. Studies in various groups of patients showed that the level of these markers reflected the severity and acuteness of the pathological process in the brain and correlated with the characteristics of the clinical symptoms of patients. The most significant for an objective assessment of the clinical status of patients and the prognosis of the course of the disease are not individual inflammatory markers, but their combinations and ratios. It was found that the quantitative change in immunological parameters was ahead of the change in clinical indicators, confirming their prognostic significance. Elevated blood markers at the stages of the disease, preceding the development of pronounced clinical symptoms, can serve as an objective criterion for the presence of a current pathological process in the brain of patients with a high risk of manifestation of endogenous psychosis. The conducted immunological studies using the “Neuro-Immuno-Test” technology revealed different activation of the immune system in patients with cognitive impairment of varying severity, i.e. from mild cognitive impairment to dementia in Alzheimer's disease (AD). Conclusion: differences in immunophenotypes, which have certain quantitative and qualitative features of the spectrum of inflammatory and autoimmune markers, found using the “Neuro-Immuno-Test”, are extremely important both for diagnosis and prognosis, and for therapy optimization.

New-onset hypertension is not associated with systemic changes in inflammatory cytokine levels

IntroductionRecent studies have suggested that hypertension develop�ment may be associated with an altered immune system. However, there is a paucity of data evaluating the association between blood pressure values and inflammatory markers in patients with new-onset hypertension.Material and methodsWe evaluated 61 subjects, including 24 healthy indi�viduals and 37 newly diagnosed hypertensive patients (aged 45 ±9.6 vs. 43.8 ±11.9 years; SBP_24hours 114 ±7.1 vs. 134.2 ±9.5 mm Hg; DBP_24hours 71.2 ±4.7 vs. 85.8 ±9.3 mm Hg, respectively) without prior antihypertensive treatment. The diagnosis of hypertension was based on 24-hour ambulatory blood pressure monitoring (ABPM). We analysed the association between blood pressure values and levels of individual inflammatory markers (ITAC, GM-CSF, fractalkine, IFN-g, IL-10, MIP-3a, IL-12, IL-13, IL-17A, IL-1b, IL-2, IL-21, IL-23, IL-5, IL-6, IL-7, IL-8, MIP-1a, MIP-1b, TNF-a, and IL-15) sepa�rately, as well as in clusters of inflammatory mediators (factor 1 – proin�flammatory: IL-1β, IL2, IL-6, IL-7, IL-12, IL-6, IL-21, TNF-α, IFN-γ; and factor 2 – anti-inflammatory: IL-13, IL-5).ResultsOur study did not show any differences in concentrations of inflam�matory markers between patients and controls. Plasma levels of inflamma�tory markers were not associated with 24-hour ambulatory blood pressure values in patients with new-onset hypertension.ConclusionsPatients with new-onset hypertension did not differ from healthy subjects regarding the levels of plasma inflammatory markers. Our findings demonstrate the need for larger, more comprehensive studies on this topic to further elucidate the relationship between hypertension and inflammation.

The inflammatory score and cardiovascular risk in young adults with overweight or obesity: The African-PREDICT study.

A complex relationship of adipokines and cytokines with cardiovascular risk motivates the use of an integrated approach to identify early signs of adiposity-related inflammation. We compared the inflammatory profiles, including an integrated inflammatory score, and cardiovascular profiles of young adults who are living with overweight and/or obesity (OW/OB). This cross-sectional study included 1194 men and women with a median age of 24.5±3.12years from the African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT). Participants were divided into approximate quartiles based on adiposity measures (body mass index, waist circumference, and waist-to-height ratio). We compared an integrated inflammatory score (including leptin, adiponectin, interleukin-6, interleukin-8, interleukin-10, and tumour necrosis factor-α) as well as the individual inflammatory markers, between extreme quartiles. We also compared blood pressure measures, left ventricular mass index, carotid-femoral pulse wave velocity, and carotid intima-media thickness between these groups. Individuals in the top quartile had worse inflammatory- and cardiovascular profiles as the integrated inflammatory score, leptin, interleukin-6, blood pressure measures, and left ventricular mass index were higher, while adiponectin was lower (all p≤0.003). Unexpectedly, carotid-femoral pulse wave velocity was also lower (p<0.001) in the top quartile. Exclusively in the top quartile, all adiposity measures related positively with the integrated inflammatory score and central systolic blood pressure (both r≥0.24; p<0.001), and negatively with interleukin-10 (all r≤-0.13; p<0.03). Of these relationships, the correlations with the integrated inflammatory score were the strongest (p<0.001). The percentage difference of being in the top quartile of all adiposity measures were higher for the inflammatory score (all≥263%), leptin (all≥175%), interleukin-6 (all≥134%), and tumour necrosis factor-α (all≥26%), and lower for adiponectin (all≥57%), interleukin-10 (all≥9%), and interleukin-8 (all≥15%) compared to being in the bottom quartile. The inflammatory score, as a comprehensive marker of adiposity-related inflammation, is strongly related to adiposity and may be an indication of early cardiovascular risk in young adults; however, further work is required to establish the clinical use thereof.

Age, sex, and inflammatory markers predict chronic conditions, cardiac disease, and mortality among captive western lowland gorillas (Gorilla gorilla gorilla).

In humans, inflammatory markers predict health risks. As great apes experience many similar conditions, measuring inflammation may provide valuable health information. We examined four serum inflammatory markers in zoo-housed gorillas (n = 48): albumin, CRP, IL-6, and TNF-α. We first analyzed age- and sex-associated patterns, then used multimodel inference to evaluate models with age, sex, and inflammatory markers as predictors of all-cause morbidity, cardiac disease, and mortality. Older gorillas had lower albumin and higher IL-6, and males had higher albumin, lower CRP, and lower TNF-α. All-cause morbidity was best predicted by age, sex, and TNF-α, but the second model containing only age and sex was equivalent. Cardiac disease was best predicted by TNF-α alongside age and sex, with lower levels associated with increased risk. When outliers were removed, the model with TNF-α was second to the model containing only age and sex. Finally, mortality risk was best predicted by the model with only age and sex. Other models containing individual inflammatory markers were within top model sets for each health outcome. Our results indicate that age and sex are robust for predicting all-cause morbidity and mortality risk in gorillas; while models which include individual inflammatory markers also predict risk, they may not improve predictions over age and sex alone. However, given the prevalence of cardiac disease in great apes, these results suggest that TNF-α warrants further investigation. With their potential to provide valuable health information, data on inflammatory markers may contribute to the care and management of gorillas in human care.

Review: Inflammation and anxiety-based disorders in children and adolescents - a systematic review and meta-analysis.

Anxiety-based disorders are common and are often chronic with an onset during childhood or adolescence. An emerging literature has examined the role of inflammation in these disorders by measuring blood concentrations of inflammatory markers such as cytokines, C-reactive protein (CRP) and immune markers such as white blood cell counts. However, existing results are inconsistent, with available meta-analyses only including adult populations. We believe this is the first systematic review and meta-analysis to investigate these inconsistencies among the population of children and adolescents. A systematic search of five electronic databases was conducted to identify studies which compared inflammatory markers between individuals with an anxiety-based disorder and healthy controls. Study quality was assessed, and pooled effect sizes (Hedges' g) were calculated using random-effects meta-analyses. Nine independent studies were identified. The combined meta-analysis of 16 cytokines and CRP was approaching significance; however, no significant between-group difference was observed for meta-analyses of individual inflammatory or immune markers. Heterogeneity was high, and quality assessments identified important limitations; primarily, small sample sizes and a lack of control over confounding variables. Although no significant effects were observed, the small number of included studies and limitations in study or reporting quality render these findings provisional. Research in this area has the potential for important clinical implications in relation to therapeutic interventions. Important recommendations for further research are put forth.

Suppression, but not reappraisal, is associated with inflammation in trauma-exposed veterans

BackgroundEmotion dysregulation can elicit inflammatory activity. The current study examined whether specific maladaptive and adaptive emotion regulation strategies were associated with inflammatory markers in trauma-exposed veterans, above and beyond PTSD. MethodsIn a cohort study, 606 participants exposed to a Criterion A trauma and recruited from Veteran Health Administration facilities completed fasting blood draws, the Emotion Regulation Questionnaire, and the Clinician Administered PTSD Scale-IV. Inflammation was assessed with high sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen levels. An inflammation index was created by summing standardized log-transformed levels of the three biomarkers. Our primary linear regression models were adjusted for sex, age, race, education, income, creatinine, and PTSD. ResultsSuppression, but not cognitive reappraisal, was significantly associated with higher levels of the inflammatory index (β = 0.14, p = 0.001). Parallel analyses for the individual inflammatory markers also showed suppression, but not reappraisal, was significantly associated with higher hsCRP (β = 0.11, p = 0.01), WBC (β = 0.11, p = 0.01), and fibrinogen (β = 0.10, p = 0.02). ConclusionsEmotional suppression is related to elevated systemic inflammation independent of PTSD. Cognitive reappraisal is unrelated to inflammation. Findings suggest over-utilization of maladaptive, rather than under-utilization of adaptive, emotion regulation strategies may be associated with systemic inflammation in trauma-exposed veterans.

VTE in ICU Patients With COVID-19

VTE in ICU Patients With COVID-19

SAT-026 Association of Inflammatory Markers with Depressive Symptoms Across the Perinatal Period

Perinatal depression (PND) is a mood disorder affecting 10-15% of women during pregnancy and postpartum. Its aetiology is complex with contribution from both genetic background and psychosocial as well as environmental stressors that determine individual responses shaped by chronic and acute disease burden (1). It is thought that the molecular basis of PND involves dysregulation of the HPA axis associated with neurotransmitter and neuroactive steroids imbalance. Inflammation appears to be a contributing mechanism, with increased levels of cytokines exerting adverse effects on serotonin metabolism, neuroplasticity and HPA hyperactivity (2). With only 50% of women detected through current screening strategies, there is an urgent unmet need for the development of biomarker-based strategies to identify women at risk of PND. In this study we used data and blood samples from the prospective Coventry and Warwickshire PND study; we investigated for inflammatory markers associated with depressive symptoms, assessed using the Edinburgh Postnatal Depression Score (EPDS) questionnaire between 24-29 weeks of gestation and again 6-10 weeks postpartum. A cut-off score of 10 categorize ‘high’ or ‘low’ risk for depression. Blood samples collected at 28 weeks of gestation were profiled for either IL-6 and IL-10 levels or a panel of 92 inflammatory markers. Individual inflammatory markers were compared across groups using Welch’s ANOVA. Results suggest that IL-10 levels were significantly correlated with EPDS score, exerting a protective effect (r= -.10), with reduced levels in the highest severity category (EPDS ≥ 15). The IL-6/IL-10 ratio was also associated with a raised EPDS score (r=.10, p=.01), as well as delivery complications (r=.09). The highest IL-6/IL-10 ratio is observed in women who had emergency caesarean section. Bayes’ theorem analysis suggested that IL-6/IL-10 ratio could be used as a negative screen to rule out low risk pregnancies. From the 92 inflammatory markers, 14 analytes were below the limit of detection for more than 50% of samples and so were excluded from further analysis. Upon comparison of groups determined by antenatal and postnatal EPDS scores, 29 markers displayed a significance value of P<0.05. Upon the application of post hoc tests, 8 markers including: STAM-BP, SIRT2, CD40, CASP8 and ADA, all associated with apoptotic processes, remained statistically significant in pregnant women with raised antenatal EPDS scores. This data support an association between inflammatory markers and perinatal depression and adverse pregnancy outcomes. Detailed quantitative analysis of such biomarker signatures at different stages of pregnancy, might lead to early detection of disease and application of targeted treatment. (1) Pariante, C. M. & Lightman, S. L. (2008) Trends Neurosci, 31 (9): 464-468. (2) Raison et al., (2006) Trends Immunol, 27 (1): 24-31.

The association between circulating levels of vitamin D and inflammatory markers in the first 2 years after colorectal cancer diagnosis.

Background:Calcitriol, the active form of vitamin D, may inhibit colorectal cancer (CRC) progression, which has been mechanistically linked to an attenuation of a pro-inflammatory state. The present study investigated the associations between circulating 25 hydroxy vitamin D3 (25(OH)D3) levels and inflammatory markers (IL10, IL8, IL6, TNFα and hsCRP) in the 2 years following CRC diagnosis.Methods:Circulating 25(OH)D3 levels and inflammatory markers were assessed at diagnosis, after 6, 12 and 24 months from 798 patients with sporadic CRC participating in two prospective cohort studies. Associations between 25(OH)D3 levels and individual inflammatory markers as well as a summary inflammatory z-score were assessed at each time point by multiple linear regression analyses. To assess the association between 25(OH)D3 and inflammatory markers over the course of 2 years, linear mixed model regression analyses were conducted.Results:Higher 25(OH)D3 levels were associated with lower IL6 levels at diagnosis, at 6 months after diagnosis and over the course of 2 years (β −0.06, 95% CI −0.08 to −0.04). In addition, 25(OH)D3 levels were inversely associated with the summary inflammatory z-score at diagnosis and over the course of 2 years (β −0.17, 95% CI −0.25 to −0.08). In addition, a significant inverse association between 25(OH)D3 levels and IL10 was found over the course of 2 years. Intra-individual analyses showed an inverse association between 25(OH)D3 and IL10, IL6 and TNFα. No statistically significant associations between 25(OH)D3 and IL8 and hsCRP levels were observed.Conclusions:Serum 25(OH)D3 levels were inversely associated with the summary inflammatory z-score and in particular with IL6 in the years following CRC diagnosis. This is of potential clinical relevance as IL6 has an important role in chronic inflammation and is also suggested to stimulate cancer progression. Further observational studies should investigate whether a possible 25(OH)D3-associated reduction of inflammatory mediators influences treatment efficacy and CRC recurrence.

CROSS-SECTIONAL AND LONGITUDINAL RELATIONSHIPS BETWEEN REST-ACTIVITY RHYTHMS AND INFLAMMATION IN OLDER MEN

Sleep disturbances and physical inactivity have been associated with chronic inflammation, an important risk factor for cognitive decline in the aging population. However most previous studies focused on the cross-sectional relationships between sleep and physical activity and inflammation. In the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study, we studied both the cross-sectional and prospective associations between characteristics of 24-hour rest-activity rhythms measured by actigraphy and inflammation index measured by multiple circulating markers. In cross-sectional analysis, a lower amplitude is associated with elevated inflammation (Odds ratio Q4 vs Q1 (95% Confidence interval): 1.65 (1.22, 2.24)). In prospective analysis, an earlier acrophase (<12:30) is associated with a two-fold increase in the risk of developing elevated inflammation over four years of follow up (2.08 (1.02, 4.23)). No individual inflammatory markers are associated with rest-activity rhythms. Our findings suggest that rest-activity rhythm characteristics predicts elevated inflammation.

Sex differences in the relationship between individual systemic markers of inflammation and pain in knee osteoarthritis

There are suggestions that the relationship between inflammation and pain in osteoarthritis (OA) may differ by sex, yet studies have been limited. We investigated whether the relationship between knee-specific OA pain and systemic inflammatory markers differs by sex. 196 patients scheduled for knee arthroplasty for OA were included. Questionnaires were completed and blood samples drawn pre-surgery. Questionnaire data: knee pain (WOMAC), sex, age, height, weight, comorbidities, depressive symptoms, and symptomatic joint count. Systemic inflammatory markers (cytokines IL-6, IL-8, IL-10, IL-1β and TNF-α) were measured by multiplex ELISA. A series of regression models with interaction terms between sex and ln-transformed inflammatory markers were estimated with pain score as the outcome. The adjusted relationship between pain and inflammatory markers, by sex, were presented graphically. Mean age was 64 years (range 43-89); females comprised 58.7% of the sample. In adjusted analyses, similar relationships between knee pain and lnIL-10 (negative: β​=​-1.28, 95%CI (-1.97, -0.58)) and lnTNF-α (positive: β​=​0.92, 95%CI (0.11, 1.76)) were found for females and males. In contrast, relationships between knee pain and lnIL-1β, lnIL-6 and lnIL-8 differed in direction for females and males. Specifically, for lnIL-1β and lnIL-8 they were positive for males, negative for females. The opposite was found with lnIL-6, negative for males, positive for females. These findings provide some evidence of sex-specific relationships between individual inflammatory markers and knee OA pain. They expose a need for further exploration of sex-differences in this context, with potential future implications for treatment or drug development in OA.

Abstract 5056: Exercise and inflammation on the risk of cancer

Abstract Introduction: High systemic inflammation and low levels of exercise are associated with increased risk of cancer. We hypothesized that in the setting of inflammation, exercise mitigates cancer risk. Methods: To address this, we identified 6,388 participants, free of cancer and cardiovascular disease, enrolled in the Multi-Ethnic Study of Atherosclerosis. Regular moderate/vigorous intentional exercise was categorized as present or absent based on self-report from validated questions. A composite inflammatory score was created with a point given for C-reactive protein, IL-6, fibrinogen, and GlycA above normal, with composite scores &amp;gt; 2 points categorized as high. Cancer incidence was ascertained based on ICD codes abstracted from hospitalization or cancer registry data. Cox proportional hazard models were used to calculate subsequent risk of incident cancer. Models were adjusted for baseline age, gender, race, pack years smoking, education, income, health insurance status, body mass index, high-density lipoprotein levels, healthy diet adherence, statin and aspirin use. Results: The mean age was 62 years (±10.2 years), 53% female, 39% white, 26% black, 22% Hispanic, and 12% Chinese-American. Compared to the reference group (individuals reporting no exercise and with low levels of inflammation), in multi-variable adjusted models, individuals with high levels of inflammation and no exercise were at highest risk of cancer (hazard ratio = 1.17; 95% confidence interval 1.00 – 1.37), while those with low levels of inflammation who exercised were at the lowest risk of cancer (HR 0.80, 95% CI 0.68-0.95). Those who had high levels of inflammation, but regular exercise had no increased risk of cancer (HR 0.94, 95% CI 0.68-1.30). There was no significant interaction between exercise and inflammation. When considering individual inflammatory markers, there was a similar pattern (Table). Conclusion: Intentional moderate/vigorous exercise may lower the risk of cancer in individuals with high versus low levels of chronic inflammation. Cox proportional hazard models for incident cancer by exercise and measures of inflammation, adjusteno exerciseany exerciseHR95% CIHR95% CILow composite score (0 - 1)Ref0.800.680.95High composite score (&amp;gt;2)1.171.001.370.940.681.30P for interaction = 0.25Low CRP (&amp;lt;2 mg/L)Ref0.800.680.95High CRP (&amp;gt;2 mg/L)1.231.051.430.980.711.35P for interaction = 0.94Low IL-6 (&amp;lt; 1.8 pg/mL)Ref0.800.680.95High IL-6 (&amp;gt;1.8 pg/mL)1.070.911.260.860.621.19P for interaction = 0.18Low GlycA (&amp;lt;400 µmol/L)Ref0.800.680.95High GlycA (&amp;gt;400 µmol/L)1.191.021.390.960.691.32P for interaction = 0.73Low fibrinogen (&amp;lt;450 mg/dL)Ref0.800.680.95High fibrinogen (&amp;gt;450 mg/dL)0.970.751.250.770.511.18P for interaction = 1.00 Citation Format: Catherine Handy Marshall, Zeina Dardari, Miguel Cainzos-Achirica, Martin B. Mortensen, Khurram Nasir, Mouaz H. Al-Mallah, Michael D. Miedema, Ron Blankstein, Roger S. Blumenthal, Kala Visvanathan, Michael J. Blaha. Exercise and inflammation on the risk of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5056.

Cytokine Response in the Pleural Fluid and Blood in Minimally Invasive and Open Esophagectomy.

Transthoracic esophagectomy for cancer triggers a massive inflammatory reaction. The data whether a minimally invasive esophagectomy (MIE) leads to less pronounced inflammatory response compared to open right-sided transthoracic esophagectomy (OE) are scarce. The aim of this study was to evaluate the extent of the inflammatory reaction, represented by levels of the pro-inflammatory interleukins IL-6 and IL-8, the anti-inflammatory IL-1 RA and the chemokines CINC-1 and MCP-1 in the right pleural fluid and the blood from patients undergoing standard OE or MIE. Pleural drainage fluid and blood was collected at five different time points during the first 72h following surgery, and the concentrations of IL-6, IL-8, IL-1 RA, CINC-1 and MCP-1 were analyzed using enzyme-linked immune-sorbent assays in 24 patients undergoing MIE or OE. The groups were matched for cancer stage and comorbidities. Pro- and anti-inflammatory mediator levels in the pleural fluid were markedly increased at the end of surgery and on postoperative days 1-3. The pleural inflammatory response of all cyto- and chemokines was lower in the MIE group, reaching significance at some time points. Cyto- and chemokine response levels measured in the blood were overall lower compared to those in the pleural fluid. The chemokines CINC-1 and MCP-1 reacted less pronounced or not at all. Preoperative pulmonary comorbidity, postoperative pulmonary morbidity and length of surgery were associated with an increased reaction in selected mediators. The minimally invasive technique attenuates the inflammatory response, especially locally in the thoracic compartment. Length of procedure, preoperative pulmonary comorbidity and postoperative pulmonary complications are mirrored in an increase in individual inflammatory markers in the pleural fluid. The value of the chemokines CINC-1 and MCP-1 as markers of inflammation in the setting of esophagectomy is unclear.

Early Inflammatory Markers for the Diagnosis of Late-Onset Sepsis in Neonates: The Nosodiag Study.

Background: Early diagnosis is essential to improve the treatment and prognosis of newborn infants with nosocomial bacterial infections. Although cytokines and procalcitonin (PCT) have been evaluated as early inflammatory markers, their diagnostic properties have rarely been compared.Objectives: This study evaluated and compared the ability of individual inflammatory markers available for clinician (PCT, semi-quantitative determination of IL-8) and of combinations of markers (CRPi plus IL-6 or quantitative or semi-quantitative determination of IL-8) to diagnose bacterial nosocomial infections in neonates.Methods: This prospective two-center study included neonates suspected of nosocomial infections from September 2008 to January 2012. Inflammatory markers were measured initially upon suspicion of nosocomial infection, and CRP was again measured 12–24 h later. Newborns were retrospectively classified into two groups: those who were infected (certainly or probably) and uninfected (certainly or probably).Results: The study included 130 infants of median gestational age 28 weeks (range, 24–41 weeks). Of these, 34 were classified as infected and 96 as uninfected. The sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (LR+ and LR-) for PCT were 59.3% (95% confidence interval [CI], 38.8–77.6%), 78.5% (95% CI, 67.8–86.9%), 48.5% (95% CI, 30.8–66.5%), 84.9% (95% CI, 74.6–92.2%), 2.7 (95% CI, 1.6–4.9), and 0.5 (95% CI, 0.3–0.8), respectively. Semi-quantitative IL-8 had the highest specificity (92.19%; 95% CI, 82.70–97.41%), PPV (72.22%; 95% CI, 46.52–90.30%) and LR+ (6.17, 95% CI, 2.67–28.44), but had low specificity (48.15%; 95% CI, 28.67–68.05%). Of all markers tested, the combination of IL-6 and CRPi had the highest sensitivity (78.12%; 95% CI, 60.03–90.72%), NPV (91.3%; 95% CI, 82.38–96.32%) and LR- (0.29; 95% CI, 0.12–0.49). The combination of IL-6 and CRPi had a higher area under the curve than PCT, but with borderline significance (p = 0.055).Conclusions: The combination of IL-6 and CRPi was superior to other methods, including PCT, for the early diagnosis of nosocomial infection in neonates, but was not sufficient for sole use. The semi-quantitative determination of IL-8 had good diagnostic properties but its sensitivity was too low for use in clinical practice.

Circulating Levels of Inflammation and the Effect on Exercise-Related Changes in Bone Mass, Structure and Strength in Middle-Aged and Older Men.

Chronic, low-grade systematic inflammation has been associated with bone loss and increased fracture risk. We previously reported that exercise improved femoral neck bone mineral density (BMD), geometry and strength and lumbar spine trabecular BMD in middle-aged and older men, but had no effect on markers of inflammation. The aim of this study was to examine the association between basal inflammatory status and the adaptive skeletal responses to exercise. Secondary analysis was completed on 91 men aged 50-79years who participated in an 18-month program of progressive resistance training plus weight-bearing impact exercise (3day/week) with and without additional calcium-vitamin D3. Markers of inflammation (serum hs-CRP, TNF-α and IL-6) and DXA and QCT-derived BMD, bone structure and strength at the lumbar spine and proximal femur were measured at baseline and 18months. Multiple regression was used to assess associations between skeletal changes and both baseline levels of individual inflammatory markers and a composite inflammatory index derived from the number of markers categorized into the highest tertile. Baseline serum hs-CRP, TNFα and IL-6 and the composite inflammatory index score were not associated with skeletal changes at any site after adjusting for age, change in lean mass, disease(s)/medication use and adherence to the exercise intervention. In conclusion, this study indicates that basal inflammatory status does not influence the osteogenic response to exercise training in healthy middle-aged and older men.

Innate immune activation and depressive and anxious symptoms across the peripartum: An exploratory study

BackgroundThere are complex associations between immune function and mental illness, yet studies in the perinatal period focus primarily on individual inflammatory markers and depressive symptoms only, cross-sectionally. We sought to examine associations between both depressive and anxious symptoms and immune activation longitudinally across the peripartum. MethodsWe measured mood (Beck Depression Inventory, BDI-1 A) and anxiety (State-Trait Anxiety Inventory, STATE) and levels of 23 cytokines at 5 points in pregnancy and postpartum in 51 women. Within subject cytokine trajectories over time by depressive and anxious symptom grouping were assessed using linear mixed effects models with random intercept and slope. We also undertook an exploratory cluster analysis based on third trimester cytokine values. ResultsBased on categorical BDI scores, IL-6 (p < 0.001), IL-15 (p = 0.047), GCSF (p = 0.003), and CCL3 (p < .001) were significantly different across time, with IL-6 (p < 0.001), IL-15 (p = 0.003), and CCL3 (p < 0.001) higher at the third trimester visit in more depressed subjects. Based on categorical STATE scores, GM-CSF significantly decreased across pregnancy for the less anxious group (p = 0.016), but not for the more anxious, and CCL3 (p = 0.017), CXCL8 (p = 0.011), and IL-6 (p < 0.001) were higher at the third trimester visit for more anxious subjects. In exploratory cluster analysis based on cytokine level, there were no differences in mood or anxiety scores, but significant differences by race/ethnicity and overweight/obesity status. Women with higher pro-inflammatory cytokine values are more likely to be Hispanics (69.2% vs. 21.4%, p = 0.015), but less likely to be African American (23.1% vs. 60.7%, p = 0.015) or overweight/obese (25% vs. 69.2%, p = 0.016) compared to women with lower pro-inflammatory cytokine values. ConclusionWe identified a pro-inflammatory burst at the third trimester, indicative of innate immune activation, in women with higher levels of both depressive and anxious symptoms, as well as differences in pro-inflammatory changes across time. We also found significant differences in cytokine levels by race, ethnicity, and overweight/obesity status. These results point the way toward future longitudinal work that considers race/ethnicity, timing, and weight status, and evaluates perinatal mood and anxiety disorders in the context of changing immune functioning across the peripartum.

Depression severity is associated with increased inflammation in veterans with peripheral artery disease.

The present study examines the association between depressive symptoms and inflammatory markers in peripheral artery disease (PAD) to better understand the mechanistic relationship between depression and PAD. A cross-sectional sample of 117 patients with PAD (97% male, 76% Caucasian) was recruited from the San Francisco Veterans Affairs Medical Center. Patients were categorized into three subgroups based upon current depressive symptom severity, as defined by Patient Health Questionnaire-8 scores: no symptoms (score of 0-4, n = 62), mild symptoms (score of 5-9, n = 33), and moderate/severe symptoms (score ≥ 10, n = 22). Serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-alpha (TNF-α) were assayed and log-transformed for multivariable analysis. To decrease the possibility of Type 1 errors, inflammatory markers were standardized and summed to create a total inflammatory score. In a multivariable analysis controlling for demographics, PAD severity, and atherosclerotic risk factors, mild and moderate/severe depressive symptoms were predictive of a higher total inflammatory score when compared to the group with no symptoms (mild symptoms p = 0.04, moderate/severe symptoms p = 0.007). Exploratory multivariable analyses of individual inflammatory markers found IL-6 levels were significantly higher in the moderate/severe symptoms group ( p = 0.006) than in the no symptoms group. Moreover, hs-CRP and ICAM-1 trended upwards with increasing depression severity. TNF-α was not associated with depression severity. We conclude that depressive symptom severity was independently associated with greater inflammation in PAD. Future research should examine the strength and directionality of this association through larger prospective cohort studies, as well as investigate the pathophysiological mechanisms responsible.

Correlation between interferon γ and interleukin 6 with PTSD and resilience

Posttraumatic Stress Disorder (PTSD) is a debilitating psychiatric disorder with decreased general health prognosis and increased mortality. Inflammation has been hypothesised to be a link between PTSD and the most common co-morbid medical disorders. However, the relationship between inflammation and PTSD is not clear. Individual inflammatory markers have shown variable associations with PTSD. This study investigates the correlations between serum cytokines, PTSD and resilience in a cohort of Caucasian Vietnam combat veterans (n = 299). After correction for multiple testing, PTSD severity was correlated with small but significant decreases in interleukin 6 and interferon γ (p = 0.004, p = 0.013, respectively) whereas resilience was correlated with increased levels of interleukin 6 and interferon γ (p = 0.023; p = 0.007, respectively). Analyses of sub-symptoms of PTSD revealed that mood and arousal symptoms showed the most significant effect on interleukin 6 and interferon γ. More research is needed to further elucidate the mechanisms underlying the relationship between cytokine levels, PTSD sub-symptoms and trauma outcomes to improve the knowledge base of differences in trauma response and the biological system.