Plasma Levels Of Inflammatory Markers Research Articles

Comparative study of high-dose Xuezhikang and low-dose Xuezhikang plus ezetimibe on pro- and anti-inflammatory markers

Aim: To investigate the effects of two different therapeutic regimes that may obtain equivalent LDL cholesterol (LDL-C) reduction (2400 mg of Xuezhikang [XZK] per day and coadministration of 600 mg of XZK plus 10 mg of ezetimibe [EZT] per day) on plasma levels of inflammatory markers in patients with dyslipidemia. Methods: A total of 46 patients with dyslipidemia were studied and were randomly divided into the two groups: group A (2400 mg XZK per day; n = 23) and group B (600 mg XZK/10 mg EZT per day; n = 23) for 6 weeks. The plasma levels of IL-6, IL-10 and CRP were analyzed at both baseline and 6 weeks. Results: Both therapy regimes resulted in similar reductions of LDL-C (p > 0.05). Compared with baseline, both treatments significantly increased plasma IL-10 and decreased IL-6, as well as CRP levels (p 0.05). Conclusion: When achieving a similar reduction in LDL-C, coadministration of low-dose XZK and EZT coul...

Inflammation and fatigue dimensions in advanced cancer patients and cancer survivors

Inflammation may underlie cancer-related fatigue; however, there are no studies that assess the relation between fatigue and cytokines in patients with advanced disease versus patients without disease activity. Furthermore, the relation between cytokines and the separate dimensions of fatigue is unknown. Here, association of plasma levels of inflammatory markers with physical fatigue and mental fatigue was explored in advanced cancer patients and cancer survivors. A total of 45 advanced cancer patients and 47 cancer survivors completed the subscales Physical Fatigue and Mental Fatigue of the Multidimensional Fatigue Inventory. Plasma concentrations of C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1-ra), interleukin-6 (IL-6), interleukin-8 (IL-8), and neopterin were measured. Nonparametric tests were used to assess differences in fatigue intensity and levels of inflammatory markers and to determine correlation coefficients between the fatigue dimensions and inflammatory markers. Compared with cancer survivors, patients with advanced cancer had higher levels of physical fatigue (median 16 vs 9, P < .001) and mental fatigue (median 11 vs 6, P = .01). They also had higher levels of all cytokines (P < .01). In advanced cancer, CRP (r = 0.49, P = .001), IL-6 (r = 0.43, P = .003), IL-1-ra (r = 0.32, P = .03), and neopterin (r = 0.25, P = .10) were correlated with physical but not with mental fatigue. In cancer survivors, only IL-1-ra was related to both physical fatigue (r = 0.24, P = .10) and mental fatigue (r = 0.35, P = .02). In advanced cancer, inflammation seems to be associated with physical fatigue, but not to mental fatigue. In cancer survivors, there was no convincing evidence that inflammation plays a major role in fatigue.

Letter by Lee Regarding Article, “Multi-Analyte Profiling Reveals MMP-9 and MPC-1 as Plasma Biomarkers of Cardiac Aging”

To the Editor: Chiao et al gained further insights of the role of plasma biomarkers in association to cardiac aging phenotypes. The authors observed significantly higher plasma levels of inflammatory markers in the senescent compared with the adult C57/BL6J mice. Among them, matrix metalloproteinase-9 (MMP9) correlated with the increase in end-diastolic dimensions that occurred with senescence. Dual labeling …

Inflammation and Behavioral Symptoms After Breast Cancer Treatment: Do Fatigue, Depression, and Sleep Disturbance Share a Common Underlying Mechanism?

Fatigue, depression, and sleep disturbance are common adverse effects of cancer treatment and frequently co-occur. However, the possibility that inflammatory processes may underlie this constellation of symptoms has not been examined. Women (N = 103) who had recently finished primary treatment (ie, surgery, radiation, chemotherapy) for early-stage breast cancer completed self-report scales and provided blood samples for determination of plasma levels of inflammatory markers: soluble tumor necrosis factor (TNF) receptor II (sTNF-RII), interleukin-1 receptor antagonist, and C-reactive protein. Symptoms were elevated at the end of treatment; greater than 60% of participants reported clinically significant problems with fatigue and sleep, and 25% reported elevated depressive symptoms. Women treated with chemotherapy endorsed higher levels of all symptoms and also had higher plasma levels of sTNF-RII than women who did not receive chemotherapy (all P < .05). Fatigue was positively associated with sTNF-RII, particularly in the chemotherapy-treated group (P < .05). Depressive symptoms and sleep problems were correlated with fatigue but not with inflammatory markers. This study confirms high rates of behavioral symptoms in breast cancer survivors, particularly those treated with chemotherapy, and indicates a role for TNF-α signaling as a contributor to postchemotherapy fatigue. Results also suggest that fatigue, sleep disturbance, and depression may stem from distinct biologic processes in post-treatment survivors, with inflammatory signaling contributing relatively specifically to fatigue.

Assessment of Atrial Conduction Time in Patients with Coronary Artery Ectasia

Coronary artery ectasia (CAE) is associated with increased sympathetic activity, plasma levels of inflammatory markers, and oxidative stress. These factors can also cause arrhythmias such as atrial fibrillation. Atrial conduction abnormalities in patients with CAE have not been investigated in terms of atrial electromechanical delay obtained by tissue Doppler echocardiography. Ninety patients with pure CAE (n = 30), nonobstructive coronary artery disease (NO-CAD) (n = 30), and angiographically normal coronary arteries "controls" (n = 30) were compared in terms of electrocardiographic P-wave measurements, echocardiographic atrial electromechanical coupling (AEC) parameters, and interatrial conduction delay. The mean left atrium diameter in the CAE group was similar to the NO-CAD group but significantly greater than the control group (3.62 ± 0.28 vs 3.46 ± 0.32 vs 3.41 ± 0.31 cm, P = 0.021). P maximum and P-wave dispersion were significantly increased in the CAE group compared to the NOCAD group and the control group (108.6 ± 6.6 vs 97.9 ± 6.6 vs 93.5 ± 6.2, P = 0.0001; 34.4 ± 7.6 vs 23.2 ± 7.8 vs 19.4 ± 7.7 ms, P < 0.0001). Mitral AEC, septal AEC, and tricuspid AEC were significantly higher in the CAE group than the NO-CAD group and the control group (68 ± 4.5 vs 57 ± 4.5 vs 53 ± 4.6 ms, P < 0.0001; 50.7 ± 7 vs 42.7 ± 7 vs 41.7 ± 7.2 ms, P = 0.0001; 47 ± 6.7 vs 39.1 ± 6.7 vs 38.1 ± 6.6 ms, P < 0.0001). Interatrial conduction delay was significantly increased in the CAE group compared to the NO-CAD group and the control group (21 ± 5.5 vs 17.8 ± 5.6 vs 15 ± 5.6 ms, P < 0.0001).The correlation analysis demonstrated that the interatrial conduction delay and P-wave dispersion (Pd) were positively correlated with number of ectatic segments (ESN) (r = 0.41, P = 0.024 vs r = 0.49, P = 0.006). Stepwise multiple linear regression analysis revealed that the ESN was the only independent determinants of interatrial conduction delay (P = 0.024). Pd and interatrial conduction delay are prolonged in patients with CAE compared to NO-CAD patients and the healthy controls.

Endothelial-Dependent Flow-Mediated Dilation in African Americans With Masked-Hypertension

Office-blood pressure (BP) measurements alone overlook a significant number of individuals with masked-hypertension (office-BP: 120/80-139/89 mm Hg and 24-h ambulatory BP monitoring (ABPM) daytime ≥135/85 mm Hg or night-time ≥120/70 mm Hg). Diminished endothelial function contributes to the pathogenesis of hypertension. To better understand the pathophysiology involved in the increased cardiovascular (CV) disease risk associated with masked-hypertension, we estimated the occurrence, assessed the endothelial function, compared plasma levels of inflammatory markers, white blood cell count (WBC count), tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hsCRP) and examined the possible relationship between endothelial function and inflammatory markers in apparently healthy prehypertensive (office-BP: 120/80-139/89 mm Hg) African Americans. Fifty African Americans who were sedentary, nondiabetic, nonsmoking, devoid of CV disease were recruited. Office-BP was measured according to JNC-7 guidelines to identify prehypertensives in whom ABPM was then assessed. Fasting plasma samples were assayed for inflammatory markers. Brachial artery flow-mediated dilation (FMD) at rest and during reactive hyperemia was measured in a subset of prehypertensives. Subjects in the masked-hypertension sub-group had a higher hsCRP (P = 0.04) and diminished endothelial function (P = 0.03) compared to the true-prehypertensive sub-group (office-BP: 120/80-139/89 mm Hg and ABPM: daytime <135/85 mm Hg or night-time <120/70 mm Hg). Regression analysis showed that endothelial function was inversely related to hsCRP amongst the masked-hypertensive sub-group (R(2) = 0.160; P = 0.04). Masked-hypertension was identified in 58% of African Americans which suggests that a masking phenomenon may exist in a sub-group of prehypertensives who also seem to have a diminished endothelial function that could be mediated by an elevated subclinical inflammation leading to the increased CV disease.

High intensity interval training reduces systemic inflammation in post-PCI patients

Increased plasma levels of inflammatory markers and markers of endothelial cell activation have been associated with increased risk for cardiovascular events. Exercise training may lower the risk for coronary heart disease by attenuating inflammation and improving endothelial function. The objective of this study was to evaluate effects of regular high-intensity exercise training on a wide range of markers of inflammation and endothelial cell activation. Consecutively, 40 patients were prospectively randomized to a 6 months supervised high-intensity interval training programme or to a control group following successful percutaneous coronary intervention (PCI). Blood samples of 36 patients with stable angina, drawn at baseline (before PCI) and at 6 months, were analysed. Late luminal loss was measured at 6 months using quantitative coronary angiography. At 6 months, levels of the inflammatory markers interleukin (IL)-6 and IL-8 were reduced and levels of the anti-inflammatory cytokine IL-10 increased in the training group only. The decrease in IL-6 and C-reactive protein levels were significantly correlated with the decrease in luminal loss following PCI. In contrast to these anti-inflammatory effects, training had no effect on markers of platelet-mediated inflammation, and the effect of training on markers on endothelial cell activation were rather complex showing attenuating (von Willebrand factor) and enhancing (E-selectin and vascular cell adhesion molecule 1) effects. Regular exercise training in stable angina patients following PCI may attenuate some, but not all, inflammatory pathways, potentially contributing to the beneficial effects of exercise training on restenosis.

Sleep Variability, Health-Related Practices, and Inflammatory Markers in a Community Dwelling Sample of Older Adults

To explore relationships between wake- and sleep-related health behaviors and circulating concentrations of inflammatory markers (interleukin [IL]-6 and tumor necrosis factor [TNF]-α) in a cohort of community dwelling older adults. Low-grade chronic inflammation is an important risk factor for age-related morbidity. Health behaviors, including average aggregate measures of sleep, have been linked to increased inflammation in older adults. Variability in sleep timing may also be associated with increased inflammation. Participants were community dwelling older adults ≥ 60 years (n = 222: 39 bereaved, 55 caregivers, 52 with insomnia, and 76 good sleepers). Mean values and intraindividual variability in sleep, as well as caffeine and alcohol use, exercise, and daytime napping, were assessed by sleep diaries. Blood samples were obtained in the morning. Several interactions were noted between sleep behaviors, inflammatory markers, and participant group. Greater variability in wake time and time in bed was associated with higher IL-6 among good sleepers relative to caregivers and older adults with insomnia. Good sleepers who consumed moderate amounts of alcohol had the lowest concentrations of IL-6 compared with the other three groups who consumed alcohol. Insomnia subjects, but not good sleepers, showed increased concentrations of IL-6 associated with caffeine use. Caregivers showed increased concentrations of TNF-α with alcohol use relative to good sleepers. Greater variability in bedtime, later wake times, and longer time in bed was associated with higher TNF-α regardless of group. Moderation and regularity in the practice of certain health behaviors, including sleep practices, were associated with lower plasma levels of inflammatory markers in older adults. Life circumstances and specific sleep disorders may modify these associations.

Oat Bran Reduces Serum Level Of Tumor Necrosis Factor - Alpha In Sedentary And Trained Rats

Acute physical exercise is known to induce a pro-inflammatory cytokine profile in the plasma. On the other hand, studies have shown that exercise training induces decreased cytokine secretion by skeletal muscle and lymphocytes. Oat-containing diets are related with diminished plasma levels of inflammatory markers; however, the effect of this supplementation on exercise-induced inflammation is controversial. PURPOSE: To analyze the effects of oat bran intake on TNF-alpha serum concentration in sedentary and trained rats. METHODS: Male Wistar rats were divided into four experimental groups: sedentary (S), sedentary receiving oat bran (SO), trained (T) and trained receiving oat bran (TO). Experimental chow was prepared from a commercial chow, which was added 30% of oat bran. Training protocol consisted in 60 minutes daily swimming, five days/ week, for eight weeks. TNF-alpha serum level was carried out by ELISA. RESULTS: TNF-alpha serum level was decreased in T (3.1-fold, p<0.05) and SO (50%, p<0.05), when compared to S. Moreover, TO showed TNF-alpha concentration minor than T (1.9-fold, p<0.05). CONCLUSION: These data show that oat bran intake induces a reduction in TNF-alpha serum level both in sedentary and trained rats, showing a modulatory effect of oat bran on the profile of this cytokine. Furthermore, the association of oat bran intake and exercise was able to induce a synergic role in reducing TNF-alpha concentration. We conclude that oat bran has a potential anti-inflammatory effect and it is able to potentiate the training-induced anti-inflammatory effect.

A polymorphism in the visfatin gene promoter is related to decreased plasma levels of inflammatory markers in patients with coronary artery disease

Visfatin, a newly identified proinflammatory adipokine, has been linked to coronary artery disease (CAD). The -1535C>T polymorphism (rs61330082) located in the visfatin gene promoter is reportedly associated with proinflammatory status. However, it is unclear whether this polymorphism correlates with plasma levels of inflammatory markers including visfatin, hs-CRP, IL-6 and TNF-α in CAD patients. The present study was to investigate the potential association of the -1535C>T polymorphism with plasma levels of visfatin, IL-6, C reactive protein (hs-CRP) and TNF-α in patients with CAD. We conducted a hospital based study with 171 CAD patients to examine the association between the -1535C>T polymorphism and plasma levels of visfatin, hs-CRP, IL-6 and TNF-α. Plasma visfatin levels were markedly different between patients with stable angina pectoris (SAP, 11.91 ± 0.70 ng/l) and those with unstable angina pectoris (UAP, 17.49 ± 0.20 ng/l) or acute myocardial infarction (AMI, 16.63 ± 0.22 ng/l; SAP versus UAP or AMI, P < 0.05). Compared with the CC genotype, variant genotypes CT and TT correlated with significantly lower levels of visfatin, hs-CRP, IL-6 and TNF-α in the SAP group (P < 0.05), with lower levels of hs-CRP and IL-6 in the UAP group (P < 0.05), and with lower levels of visfatin in the AMI group (P < 0.05) after adjustment for age, gender, smoking, hypertension, diabetes, dyslipidemia and medication. Our results suggest that the -1535C>T polymorphism is associated with decreased plasma levels of inflammatory markers in CAD patients, reflecting that this polymorphism might provide a useful marker for predicting the development of CAD events.

Peroxisome Proliferator-Activated Receptor-γ (PPARγ) Agonist Improves Coronary Artery Endothelial Function in Diabetic Patients with Coronary Artery Disease

The aim of this study was to assess the effect of rosiglitazone on endothelial function of the coronary arteries and on plasma levels of inflammatory markers in diabetic patients with coronary artery disease (CAD). Fifty-six patients with type 2 diabetes and CAD were randomized to receive either rosiglitazone (4 mg/day) or a control for 12 weeks. The coronary flow velocity reserve (CFVR) was assessed using transthoracic Doppler echocardiography at baseline and after 12 weeks. After 12 weeks of rosiglitazone treatment, plasma levels of C-reactive protein were significantly decreased and the median CFVR was significantly increased compared with baseline levels and compared with the control group. These results suggest that, in addition to its beneficial metabolic effects, rosiglitazone, via its anti-inflammatory effects, may improve endothelial function of the coronary arteries in patients with diabetes and CAD.

The Polymorphism in Aldehyde Dehydrogenase-2 Gene Is Associated with Elevated Plasma Levels of High-Sensitivity C-Reactive Protein in the Early Phase of Myocardial Infarction

Aldehyde dehydrogenase-2 (ALDH2) is a key enzyme of alcohol metabolism, catalyzing the conversion of aldehyde to acetic acid. The G-to-A polymorphism in exon 12 of the ALDH2 gene, which causes Glu-to-Lys substitution at codon 504, has been shown to be an independent risk factor for acute myocardial infarction (AMI). We investigated the possible role of the G-to-A polymorphism in the severity of the myocardial damage in the early phase of AMI by measuring plasma levels of inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP). A total of 226 Han Chinese patients with AMI were divided into two groups: subjects without A allele (GG, n = 144) and subjects with A allele (GA and AA, n = 82), and the blood samples were collected within 12 hours after the onset of AMI. The results displayed that high-density lipoprotein cholesterol (HDL-C) was higher in GG group than that in GA and AA group (p < 0.05). The body mass index (BMI) and the concentration of hs-CRP were lower in GG group than that in GA and AA group (p < 0.05). Multivariate logistic regression analysis showed that subjects with the A allele were at an increased risk for the high level of hs-CRP (> 3 mg/L) compared with those with GG genotype (OR = 4.908, 95% CI = 1.57 approximately 20.98). Thus, the A allele in ALDH2 gene is associated with the elevated plasma levels of hs-CRP after the onset of AMI, suggesting a higher susceptibility of the myocardium to ischemic injuries.

Low plasma levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNFα), and vascular endothelial growth factor (VEGF) in patients with alpha1-antitrypsin deficiency-related fibromyalgia

Abnormalities in blood inflammatory markers have been associated with clinical manifestations and the pathogenesis of the fibromyalgia syndrome (FMS); a relationship between inherited alpha1-antitrypsin deficiency (AATD) and FMS has also been recently raised. In this study, plasma levels of inflammatory markers in FMS patients with and without AATD have been investigated. Blood samples from 138 age-matched females (79 FMS) and 59 general population (GP), with normal MM [n = 82 (59.4%)] and with MS, MZ, SZ, and ZZ AATD genotypes [n = 56 (40.6%)], were analyzed by ELISA for monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNFalpha), soluble TNFalpha receptors I and II, interleukin-8, and vascular endothelial growth factor (VEGF). Plasma levels of MCP-1, VEGF, and TNFalpha were significantly lower in FMS and GP subjects with AATD compared with those with normal MM-AAT genotypes. Moreover, plasma levels of MCP-1, VEGF, and TNFalpha were lower in AATD subjects with FMS than in those without FMS (P = 0.000, 0.000, and 0.046, respectively). No statistical differences were found for the other substances measured. Furthermore, a logistic regression model based on plasma MCP-1 cutoff value of <or=130 pg/ml allowed us to discriminate between FMS and GP subjects with a sensitivity of about 93% and a specificity of 79%. Low plasma levels of MCP-1, VEGF, and TNFalpha are related to AATD, although more markedly in FMS patients. Thus, hypotheses considering FMS as an inflammatory condition related to high plasma levels of inflammatory biomarkers cannot be supported.

Relationship between plasma inflammatory markers and plaque fibrous cap thickness determined by intravascular optical coherence tomography

ObjectiveThe purpose of this study was to evaluate the relationship between human plaque fibrous cap thickness detected by intravascular optical coherence tomography (OCT) and the plasma levels of inflammatory factors...

Randomized clinical trial of folate supplementation in patients with peripheral arterial disease

The aim was to determine whether folate supplementation improved arterial function in patients with peripheral arterial disease (PAD). Individuals with PAD were randomly assigned to receive 400 microg folic acid (45 patients) or 5-methyltetrahydrofolate (5-MTHF) (48) daily, or placebo (40) for 16 weeks. Primary endpoints were changes in plasma total homocysteine (tHcy), ankle : brachial pressure index (ABPI) and pulse wave velocity (PWV). Secondary outcomes were changes in plasma inflammatory markers. Plasma tHcy was significantly reduced in folic acid and 5-MTHF groups compared with controls: median difference: - 2.12 (95 per cent confidence interval - 3.70 to - 0.75) micromol/l (P = 0.002) and - 2.07 (-3.48 to - 0.54) micromol/l (P = 0.007) respectively. ABPI improved significantly: median difference 0.07 (0.04 to 0.11) (P < 0.001) and 0.05 (0.01 to 0.10) (P = 0.009) respectively. Brachial-knee PWV (bk-PWV) decreased significantly in individuals receiving 5-MTHF and tended to be reduced in those taking folic acid compared with controls: median difference: - 1.10 (-2.20 to - 0.20) m/s (P = 0.011) and - 0.90 (-2.10 to 0.00) m/s (P = 0.051) respectively. Plasma levels of inflammatory markers were not affected. Folate administration reduced plasma homocysteine, and slightly improved ABPI and bk-PWV.

Biglycan expression in hypertensive subjects with normal or increased carotid intima-media wall thickness

Background Biglycan (BGN), an extracellular matrix proteoglycan, has been shown to convey pro-inflammatory signals. In the present study we investigated BGN expression and its correlation with plasma levels of inflammatory markers in hypertensive subjects with or without alteration of carotid intima media thickness (IMT). Methods We evaluated 123 untreated essential hypertensives with no additional risk factors for atherosclerosis nor signs of cardiovascular disease and 40 controls. Hypertensives were classified according to a normal (≤ 1 mm) or increased (> 1 mm) IMT. BGN-mRNA and protein expression were measured in unstimulated, LPS- and Angiotensin II (Ang-II)-stimulated blood monocytes. Plasma concentrations of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and high sensitivity-C-reactive protein (hs-CRP) were also measured. Results We found increased levels of IL-6, TNF-α, hs-CRP, and BGN-mRNA and protein in hypertensives vs controls (1.72 ± 0.60 vs 1 n-fold, and 3.60 ± 0.75 vs 1 n-fold, both p < 0.001). However, BGN expression was not significantly different between hypertensives with IMT ≤ 1 mm and > 1 mm. Furthermore, in vitro addition of Ang II enhanced basal BGN-mRNA (in hypertensives: 3.57 ± 1.08 vs 1.72 ± 0.60 n-fold, p < 0.001) and protein (in hypertensives: 4.92 ± 0.42 vs 3.41 ± 0.75, p < 0.001) expression in monocytes. Conclusions Our data provide evidence of an enhanced expression of BGN in essential hypertension. In addition we suggest that Ang II can mediate monocyte BGN production.

Periodontal Therapy Reduces Plasma Levels of Interleukin‐6, C‐Reactive Protein, and Fibrinogen in Patients With Severe Periodontitis and Refractory Arterial Hypertension

Recent epidemiologic studies suggest that inflammation is the link between periodontal diseases and cardiovascular complications. This study aimed to evaluate the effects of non-surgical periodontal treatment on plasma levels of inflammatory markers (interleukin [IL]-6, C-reactive protein [CRP], and fibrinogen) in patients with severe periodontitis and refractory arterial hypertension. Twenty-two patients were examined and randomly divided into two groups. The test group was composed of 11 patients (mean age, 48.9 +/- 3.9 years) who received periodontal treatment, whereas the control group had 11 patients (mean age, 49.7 +/- 6.0 years) whose treatment was delayed for 3 months. Demographic and clinical periodontal data were collected, and blood tests were performed to measure the levels of IL-6, CRP, and fibrinogen at baseline and 3 months later. The clinical results showed that the mean percentages of sites with bleeding on probing, probing depth (PD) 4 to 5 mm, PD > or =6 mm, clinical attachment loss (CAL) 4 to 5 mm, and CAL > or =6 mm were significantly reduced in the test group 3 months after periodontal treatment. There were no significant differences between the data at baseline and 3 months in the control group. Periodontal treatment significantly reduced the blood levels of fibrinogen, CRP, and IL-6 in the test group. Non-surgical periodontal therapy was effective in improving periodontal clinical data and in reducing the plasma levels of IL-6, CRP, and fibrinogen in hypertensive patients with severe periodontitis.

Differential effects of isoflurane and CO 2 inhalation on plasma levels of inflammatory markers associated with collagen-induced arthritis in DBA mice

Inhalation of CO 2 or isoflurane is a commonly used method of euthanasia with mice, but information related to their effects on serum inflammatory markers in chronic models of inflammation is limited. In the current study, nineteen-week old DBA female mice with ( n = 53) or without ( n = 51) collagen-induced arthritis were randomly assigned to euthanization with CO 2 ( n = 55) or isoflurane ( n = 49. Plasma was collected for the measurement of soluble intercellular adhesion molecule-1 (sICAM-1), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) by ELISA. When mice without and with collagen-induced arthritis were pooled, compared to CO 2, administration of isoflurane was associated with lower production of the pro-inflammatory cytokines TNF-α (pg/ml, mean ± SEM) (26.1 ± 2.82 versus 48.1 ± 7.99) and IL-6 (25.18 ± 2.73 versus 48.1 ± 6.82) (ANOVA, p < 0.05). In contrast to TNF-α and IL-6, administration of CO 2 decreased the plasma sICAM-1 level (1170 ± 50 versus 758 ± 24 for CO 2) ( p < 0.00001). When data were analyzed as a function of collagen-induced arthritis, the differences between CO 2 and isoflurane persisted. Low plasma sICAM-1 levels found in CO 2 euthanasia group may be due to degradation. Since mice are the most common animal model for studying inflammation, researchers should be aware of these iatrogenic experimental variables before interpreting their data.

Relationship between sympathetic nervous activity and inflammatory response after subarachnoid hemorrhage in a perforating canine model

The objective of the present study was to evaluate the correlation between sympathetic nerve activation and inflammatory response in the acute stage of subarachnoid hemorrhage (SAH) in a canine perforating model. SAH was induced by perforation of the basilar artery with the use of a microcatheter via the femoral artery in 20 mongrel dogs. Hemodynamic parameters and intracranial pressure were recorded, and blood sample for C3a, C5b-9, IL-6, IL-8 and noradrenaline kinetic determination were measured at 0, 5, 15, 30, 60, 120, and 180 min after SAH. Noradrenaline (pg/mL) increased abruptly from 104 ± 59 to 2010 ± 918 at 5 min after SAH. C3a and C5b-9 reached peak values at 15 min and IL-6 and IL-8 reached peak values at 30 min after SAH, respectively. The peak values of C3a and C5b-9 correlated positively with the peak value of noradrenaline ( r = 0.743 and r = 0.753, respectively). The peak values of IL-6 and IL-8 also correlated positively with the peak values of noradrenaline ( r = 0.603 and r = 0.681, respectively).These results suggest that a pronounced activation of the sympathetic nervous system and the inflammatory response occurs in acute stage of SAH. Significant association between the rate of spillover of norepinephrine to plasma and the plasma levels of inflammatory markers indicates that the two processes, sympathetic activation and immune response are quantitatively linked in early stage after SAH. The exact mechanisms underlying this phenomenon deserved further investigations.

Interleukin-1 Receptor Antagonist and Incident Depressive Symptoms Over 6 Years in Older Persons: The InCHIANTI Study

We test the hypothesis that in older persons higher plasma levels of inflammatory markers predict the development of depressive symptoms during a 6-year follow-up. This study is part of the InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) study, a prospective population-based study of older persons. The sample consisted of 991 participants, ages 65 years and older. Serum levels of C-reactive protein, interleukin (IL)-1beta, IL-1 receptor antagonist (ra), tumor necrosis factor-alpha, IL-6, IL-6 receptor, and IL-18 were measured. Depressive symptoms were assessed at baseline and at the 3- and 6-year follow-ups with the Center for Epidemiological Studies-Depression Scale (CES-D). Depressed mood was defined as CES-D > 20. Potential confounders were baseline variables related to sociodemographic, somatic health, and functional status. At baseline, IL-1ra levels were significantly higher (p = .004) in depressed compared with nondepressed participants. After adjustment for confounders, among subjects free of depression at baseline, those in the third and fourth IL-1ra quartiles compared with those in the lowest quartile had, respectively, a 2.32-fold (95% confidence interval: 1.21-4.42, p = .01) and 2.78-fold (95% confidence interval: 1.47-5.26, p = .002) higher risk of developing depressed mood during a 6-year follow-up. In old age, persons with high plasma levels of IL1-ra had a higher risk of developing depressive symptoms over time. These findings suggest a potential causal role for inflammation in the development of depressive symptoms in older persons.