Log-transformed IL-6 Research Articles

Predictive inflammatory biomarkers for change in suicidal ideation in major depressive disorder and panic disorder: A 12-week follow-up study

Previous studies have investigated the role of inflammatory markers in suicidality of patients with major depressive disorder (MDD) or panic disorder (PD). However, few studies have investigated associations between serum inflammatory cytokine levels and suicidality. We hypothesized that MDD and PD status might be significantly associated with serum inflammatory cytokines and that we could predict levels of improvement in suicide ideation intensity using serum inflammatory biomarkers in patients with MDD and PD. For this study, 41 patients with MDD, 52 patients with PD, and 59 healthy control (HC) subjects were enrolled. Psychological measurements and serum inflammatory markers such as interleukin (IL) −6, −10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and C reactive protein (CRP) were examined. A total of five visits were completed during 12 weeks. After controlling for confounding factors, log-transformed IL-6 (ln_IL-6) at baseline (MDD: 0.297 ± 0.626; PD: 0.342 ± 0.723; HC: −0.121 ± 0.858; p = 0.007, >0.0017, 0.05/30) and mean ln_IL-6 (MDD: 0.395 ± 0.550, PD: 0.249 ± 0.544, HC: −0.139 ± 0.622, p = 0.002, >0.0017, 0.05/30) levels were trends towards significantly higher in patients with MDD and PD than in HC. In MDD patients, a higher level of basal ln_TNF-α was a significant predictor of ΔSSI (changes in SSI scores between baseline and week 12) even after controlling for changes of depression symptoms and baseline SSI scores (standardized β = 0.541, p = 0.002 < 0.0028, 0.05/18). In conclusion, we could predict ΔSSI using baseline inflammatory biomarkers for patients with MDD.

The Association of Aging Biomarkers, Interstitial Lung Abnormalities, and Mortality.

Rationale: The association between aging and idiopathic pulmonary fibrosis has been established. The associations between aging-related biomarkers and interstitial lung abnormalities (ILA) have not been comprehensively evaluated.Objectives: To evaluate the associations among aging biomarkers, ILA, and all-cause mortality.Methods: In the FHS (Framingham Heart Study), we evaluated associations among plasma biomarkers (IL-6, CRP [C-reactive protein], TNFR [tumor necrosis factor α receptor II], GDF15 [growth differentiation factor 15], cystatin-C, HGBA1C [Hb A1C], insulin, IGF1 [insulin-like growth factor 1], and IGFBP1 [IGF binding protein 1] and IGFBP3]), ILA, and mortality. Causal inference analysis was used to determine whether biomarkers mediated age. GDF15 results were replicated in the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) Study.Measurements and Main Results: In the FHS, there were higher odds of ILA per increase in natural log-transformed GDF15 (odds ratio [95% confidence interval], 3.4 [1.8-6.4]; P = 0.0002), TNFR (3.1 [1.6-5.8]; P = 0.004), IL-6 (1.8 [1.4-2.4]; P < 0.0001), and CRP (1.7 [1.3-2.0]; P < 0.0001). In the FHS, after adjustment for multiple comparisons, no biomarker was associated with increased mortality, but the associations of GDF15 (hazard ratio, 2.0 [1.1-3.5]; P = 0.02), TNFR (1.8 [1.0-3.3]; P = 0.05), and IGFBP1 (1.3 [1.1-1.7]; P = 0.01) approached significance. In the COPDGene Study, higher natural log-transformed GDF15 was associated with ILA (odds ratio, 8.1 [3.1-21.4]; P < 0.0001) and mortality (hazard ratio, 1.6 [1.1-2.2]; P = 0.01). Causal inference analysis showed that the association of age with ILA was mediated by IL-6 (P < 0.0001) and TNFR (P = 0.002) and was likely mediated by GDF15 (P = 0.008) in the FHS and was mediated by GDF15 (P = 0.001) in the COPDGene Study.Conclusions: Some aging-related biomarkers are associated with ILA. GDF15, in particular, may explain some of the associations among age, ILA, and mortality.

794: Life course psychosocial stress exposure associated with hypertensive disorders of pregnancy

Hypertensive disorders of pregnancy (HDP) complicate 5-10% of all pregnancies and are a major cause of pregnancy-related morbidity. Exposure to psychosocial stress has been associated with systemic inflammation and adverse birth outcomes in pregnant women. The primary objective of this analysis was to determine if a woman’s psychosocial stress exposure across her life course was associated with an increased risk for development of HDP. Additionally, we examined whether serum inflammation was an underlying biological mediator for this relationship. A multi-site prospective study was conducted in a socio-demographically diverse cohort of 647 pregnant women. In a study visit between 12 and 10 6/7 weeks’ gestation, maternal psychosocial stress was assessed with six validated assessments and inflammation was measured via log-transformed serum concentrations IFNγ, IL-10, IL-13, IL-6, IL-8, and TNFα. A composited stress score was calculated for each participant from the six stress assessments. The diagnosis of HDP was abstracted from the medical record and was defined as the presence of gestational hypertension after 20 weeks of pregnancy and/or preeclampsia. The association between composite stress and HDP was determined with univariate and multivariate logistic regression. Inflammation, using the six inflammatory biomarkers, was tested as a potential mediator between stress and HDP. Participants with higher composite stress scores were more likely to develop HDP (OR 1.50, 95% CI 1.06 – 2.12) (Table 1). When adjusted for known risk modifiers of HDP, including maternal age, race/ethnicity, parity, pre-pregnancy BMI, diabetes, chronic hypertension, and smoking during pregnancy, the risk remained relatively unchanged (OR 1.50, 95% CI 1.03 – 2.20). No mediation effect by inflammation was observed. Independent of known risk factors, women exposed to greater composite stress burden across the life course are at increased risk of developing HDP. Future work should further investigate biologic mechanisms linking life course stress exposure and HDP.

Association Between Inflammatory Markers and Myocardial Fibrosis.

Inflammation promotes adverse ventricular remodeling. T1 mapping has been used to noninvasively assess interstitial myocardial fibrosis. We examined the association of baseline markers of systemic inflammation with interstitial myocardial fibrosis measured by extracellular volume fraction (ECV) and native T1 mapping at 10-year follow-up in the MESA (Multi-Ethnic Study of Atherosclerosis). Seven hundred seventy-two participants had complete baseline data and underwent cardiac magnetic resonance imaging. All analyses were stratified by sex. Multivariable linear regression models were constructed to assess the associations of baseline CRP (C-reactive protein), IL (interleukin)-6, and fibrinogen with native T1 time and ECV. Longer native T1 times and higher percentages of ECV represent increasing myocardial fibrosis. A 1-SD increment of log-transformed IL-6 levels was associated with 0.4% higher ECV in men (β=0.4; P=0.05). CRP and fibrinogen were not associated to ECV. A 1-SD increment in the log-transformed CRP levels was associated with 4.9 ms higher native T1 (β=4.9; P=0.03). In women, the inflammatory markers did not demonstrate association with native T1 nor ECV. Higher IL-6 and CRP levels are associated with increased interstitial myocardial fibrosis assessed by cardiac magnetic resonance in men. However, no inflammatory markers were associated to myocardial fibrosis in women.

Rapid inflammation modulation and antidepressant efficacy of a low-dose ketamine infusion in treatment-resistant depression: A randomized, double-blind control study

Increasing evidence supports the rapid antidepressant effect of a low-dose ketamine infusion in treatment-resistant depression (TRD). Proinflammatory cytokines play a crucial role in the pathophysiology of TRD. However, it is unknown whether the rapid antidepressant effect of ketamine is related to the rapid suppression of proinflammatory cytokines. Seventy-one patients with TRD were randomized into three groups according to the treatment received: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and normal saline infusion. Proinflammatory markers, including C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α were examined at baseline and at 40 min, 240 min, Day 3, and Day 7 postinfusion. Montgomery–Åsberg Depression Rating Scale (MADRS) was assessed for depressive symptoms across time. Log-transformed IL-6 and TNF-α levels differed significantly over time. The decrease in TNF-α between baseline and 40 min postinfusion was positively correlated with a decrease in MADRS scores across time in the 0.5 mg/kg ketamine group. This is the first clinical study to support a positive correlation between changes in cytokine levels after ketamine infusion and improvements in depressive symptoms with TRD. The rapid suppression of proinflammatory cytokines may contribute to the rapid antidepressant effect of the ketamine infusion.

ASSESSMENT OF SYSTEMIC INFLAMMATION MARKERS IN HIV INFECTED OPIATE USERS

Interleukin 6 and D-dimer known as chronic systemic inflammation markers shown prognostic significance in course of HIVdisease. Association between opioid use and systemic inflammation response are still elucidate. Objective: аssess plasma levels of IL-6 and D-dimer in HIV-positive patients in groups formed on the base of opiate use activity. Materials and methods. Crosssectional study of 346 HIV-positive ART-naive individuals. Participants were categorized into 3 groups according to their history of opioid use: 1) current opioid use — past 30 day opioid use; 2) «ever» opioid use — no use in past 30 days; 3) «never» opioid use. Results. Рarticipants with current opioid use had higher log-transformed IL-6 (0,4 [ s 1,0]; p&lt;0,0001) and D-dimer (-0,6 [ s 0,9]; p&lt;0,0001) levels than participants who reported «ever» (-0,1 [ s 1,0] and -0,9 [ s 0,8]), or «never» (-0,4 [ s 0,7] and 1,3 [ s 0,7]) opioid use. Conclusion. Оpioid use in HIV-positive participants is associated with higher inflammatory response.

Maternal serum cytokine levels and risk of bipolar disorder

Prenatal exposure to influenza has previously been associated with increased risk of bipolar disorder (BD), an association that may be mediated by maternal cytokines. The objective of this study was to determine the association between maternal levels of cytokines measured during each trimester of pregnancy and the risk of BD in offspring. We conducted a case-control study nested in the Child Health and Development Study, a birth cohort that enrolled pregnant women in 1959–1966. Potential cases with DSM-IV-TR bipolar I disorder, bipolar II disorder, BD not otherwise specified, and BD with psychotic features were ascertained through electronic medical records, a public agency database, and a mailing to the cohort. Diagnoses were confirmed by clinical interview. Nine cytokines (IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and GM-CSF) were measured simultaneously by Luminex assays in archived prenatal maternal serum samples from 85 cases and 170 matched controls. Data were analyzed using conditional logistic regression. In the overall study sample, there were no significant associations between prenatal maternal cytokine levels and BD after adjustment for confounders. The risk of BD without psychotic features was decreased among subjects with higher maternal levels of first trimester log-transformed IL-4 (OR (95% CI)=0.76 (0.58, 0.98); p=0.04) and third trimester log-transformed IL-6 (OR (95% CI)=0.64 (0.42, 0.98); p=0.04). In conclusion, higher levels of prenatal maternal cytokines were not associated with increased risk for BD. Further studies with larger samples are necessary to confirm the finding.

Association between plasma leptin level and systemic inflammatory markers in patients with aggressive periodontitis.

Background:Increasing evidence supports an association between periodontitis and systemic diseases. Leptin is involved both in the energy metabolism and inflammatory processes and is suggested to be a link between periodontal infection and systemic health. The present study aimed to evaluate the peripheral leptin concentration in patients with aggressive periodontitis (AgP) and to explore the relationship between leptin and systemic inflammation.Methods:Ninety patients with AgP visiting the Clinic of the Periodontology Department, Peking University School and Hospital of Stomatology between July 2001 and May 2006, and 44 healthy controls (staff and student volunteers in the same institute) were recruited. Plasma levels of leptin and inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay. Correlation and multiple linear regression analysis were performed to analyze the association between plasma leptin level and other variables.Results:Plasma leptin level of AgP group was significantly higher than that of the control group (19.7 ± 4.4 ng/ml vs. 7.5 ± 1.3 ng/ml, P < 0.01). After controlling for age, gender, and body mass index, positive correlation was observed between plasma leptin concentration and log-transformed levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and CRP), and the partial correlation coefficients ranged from 0.199 to 0.376 (P < 0.05). Log-transformed IL-1β and IL-6 levels entered the final regression model (standardized β were 0.422 and 0.461 respectively, P < 0.01).Conclusions:Elevated plasma leptin concentration may be associated with increased systemic levels of inflammatory markers in AgP patients.

Predictive value of circulating interleukin-6 and heart-type fatty acid binding protein for three months clinical outcome in acute cerebral infarction: multiple blood markers profiling study

IntroductionThere is no single blood marker for predicting the prognosis in ischemic stroke. A combination of multiple blood markers may enhance the ability to predict long-term outcome following ischemic stroke.MethodsBlood concentrations of neuronal markers (neuron-specific enolase, visinin-like protein 1, heart type fatty acid binding protein (hFABP) and neuroglobin), astroglial markers (S100B and glial fibrillary acidic protein), inflammatory markers (IL-6, TNF-α, and C-reactive protein), blood-brain barrier marker (matrix metalloproteinase 9), and haemostatic markers (D-dimer and PAI-1) were measured within 24 hours after stroke onset. The discrimination and reclassification for favorable and poor outcome were compared after adding individual or a combination of blood markers to the clinical model of stroke outcome.ResultsIn multivariate analysis, natural log-transformed (log) IL-6 (odds ratio (OR): 1.75, 95% CI: 1.25 to 2.25, P = 0.001) and loghFABP (OR: 3.23, 95% CI: 1.44 to 7.27, P = 0.005) were independently associated with poor outcome. The addition of a single blood marker to the clinical model did not improve the discriminating ability of the clinical model of stroke outcome. However, the addition of the combination of logIL-6 and loghFABP to the clinical model showed improved discrimination (area under receiver operating characteristic (AUROC) curve: 0.939 versus 0.910, P = 0.03) and reclassification performance (net reclassification improvement index: 0.18, P = 0.005).ConclusionsA combination of circulating IL-6 and hFABP level has an additive clinical value for the prediction of stroke outcome.

Elevated Levels of Interleukin 6 and C‐Reactive Protein Associated With Cognitive Impairment in Heart Failure

There is abundant evidence on inflammatory mechanisms in heart failure (HF) that are used for prognostication of the disease; however, data are lacking regarding the association between elevated cytokines, C-reactive protein (CRP), and cognition in HF. A cross-sectional pilot study of 38 patients with HF, aged 62 years (standard deviation± 9 years), predominantly men (68%) and Caucasian (79%) were screened for cognitive function using the Montreal Cognitive Assessment (MoCA). The study aimed to examine cognitive scores on MoCA with cytokines, interleukin 6 [IL-6] and tumor necrosis factor α [TNF-α], and CRP as indicators of early cognitive changes in HF. The result showed no direct correlation between cardiac variables and the MoCA score. The MoCA score, however, was inversely associated with IL-6 (r=-0.53, P=.001) and CRP (r=-0.34, P=.04), with no association to TNF-α. Regression analysis on the MoCA score and log-transformed IL-6 accounted for an additional 11% variation and remained statistically significant (P=.008) after controlling for covariates of education, living arrangements, and loneliness. The large effect size (R(2) =0.87) found in this pilot study provides rationale for a larger exploratory study to examine associations between cognitive function, cytokines, and CRP levels and help design future intervention studies.

Long-Term Resistance Training Is Associated with Reduced Circulating Levels of IL-6, IFN-Gamma and TNF-Alpha in Elderly Women

Objective: The increase in inflammatory activity associated with aging is a characteristic of chronic disease processes that accounts for most of the mortality in the elderly. Resistance training (RT) has been shown to promote metabolic and functional benefits in this population. The objective of this study was to investigate the association between long-term RT and circulating levels of the proinflammatory mediators IL-6, TNF-α and IFN-γ in elderly women. Methods: This cross-sectional study included 54 older outpatients divided into a group that underwent RT (n = 28) for an average of 8.6 ± 0.3 months and a sedentary group (n = 26). Measurements were taken only at the end of the intervention, and cytokine values were log-transformed. Dietary intake was controlled as a confounding factor. Results: The RT group presented reduced levels of log₁₀IFN-γ (approx. 45%; p = 0.003), log₁₀IL-6 (approx. 30%; p = 0.002) and log₁₀TNF-α (approx. 22%; p = 0.036). Total caloric intake and systolic arterial blood pressure were significantly lower in the RT group (p = 0.001 and p = 0.022, respectively). Pearson’s product moment correlation test revealed a negative association between the fat-free mass (FFM) index and log-transformed IL-6 levels (p = 0.03; n = 54) and a trend towards significance for the correlation between the FFM index and log₁₀IFN-γ (p = 0.05; n = 54). Conclusion: Long-term, moderate-intensity RT in elderly women is associated with lower circulating levels of cytokines that are potentially implicated in disorders associated with physical inactivity and aging.

Association of High-Molecular-Weight to Total Adiponectin Ratio with Pulse Wave Velocity in Hemodialysis Patients

High-molecular-weight adiponectin (HMW ADPN) plays an important role in the regulation of insulin action and atherogenic processes, but the role of HMW ADPN remains to be determined in hemodialysis (HD) patients. In this study, we measured serum total and HMW ADPN in 67 HD patients (age: 67 ± 14 years, time on HD: 75 ± 68 months, male/female = 39/28), and examined an association between HMW ADPN and arteriosclerotic parameters such as aortic pulse wave velocity (PWV), cardio-ankle vascular index (CAVI) and ankle-brachial pressure index (ABI). PWV was significantly correlated positively with log-transformed IL-6 (r = 0.33, p < 0.01). CAVI was significantly related to the percentile of aortic calcification area (%ACA) (r = 0.28, p = 0.03) and log-transformed IL-6 (r = 0.25, p = 0.05). ABI was associated negatively with log-transformed IL-6 (r = –0.35, p < 0.01) and %ACA (r = –0.36, p < 0.01), but positively with albumin (r = 0.33, p < 0.01). The HMW-to-total ADPN ratio, a better predictor for insulin resistance, was significantly and positively correlated with PWV (r = 0.34, p < 0.01) and CAVI (r = 0.24, p = 0.05). A multiple stepwise regression analysis revealed that the HMW-to-total ADPN ratio was an independent determinant for PWV and CAVI but not for ABI. The findings suggest that HMW-to-total ADPN ratio may be positively associated with aortic stiffness in HD patients.

Inflammatory Markers and Loss of Muscle Mass (Sarcopenia) and Strength

Purpose The objective of this study was to investigate whether high levels of serum interleukin (IL)-6, C-reactive protein (CRP), and α1-antichymotrypsin (ACT) were associated with the loss of muscle strength or muscle mass (sarcopenia) in older persons. Subjects The study included 986 men and women of the Longitudinal Aging Study Amsterdam, with a mean age of 74.6 years (standard deviation 6.2). Methods Grip strength (n = 986) and appendicular muscle mass (n = 328, using dual-energy x-ray absorptiometry) were obtained in 1995 and 1996 and repeated after a 3-year follow-up. Loss of muscle strength was defined as a loss of grip strength greater than 40%, and sarcopenia was defined as a loss of muscle mass greater than 3%, approximating the lowest 15% of the study sample. Results Multiple linear and logistic regression analyses revealed that higher levels of IL-6 were associated with greater decline in muscle strength, which decreased by −3.21 kg (standard error 0.81) per standard deviation increase in log-transformed IL-6. After adjustment for confounders, including sociodemographic, health, and lifestyle factors, high IL-6 (>5 pg/mL) and high CRP (>6.1 μg/mL) were associated with a 2 to 3-fold greater risk of losing greater than 40% of muscle strength. Persons with high levels of ACT (>181% of the normal human pooled plasma) were 40% less likely to experience loss of muscle strength and tended ( P = .07) to have a smaller decline in muscle mass compared with those in the lowest quartile of ACT. No consistent associations of IL-6 and CRP with sarcopenia were found. Conclusion The findings of this prospective, population-based study suggest that higher levels of IL-6 and CRP increase the risk of muscle strength loss, whereas higher levels of ACT decrease the risk of muscle strength loss in older men and women.