Presence Of Low-grade Systemic Inflammation Research Articles

Evaluation of systemic immune inflammation index and neutrophil-to-lymphocyte ratio in schizophrenia, bipolar disorder and depression.

Numerous studies consistently report on the frequent presence of low-grade systemic inflammation in individuals with schizophrenia, bipolar disorder (BD), and depression. Neutrophil-to-lymphocyte ratio (NLR) and arecently established marker, systemic immune inflammation index (SII), are markers used to assess systemic inflammation and immune response. In this study, NLR and SII index values were examined and compared across patients diagnosed with major psychiatric disorders and healthy controls. The study included, totaling 129 patients, encompassed individuals who were diagnosed with schizophrenia in remission or BD in the euthymic period, and those undergoing treatment for major depressive disorder (MDD). The control group consisted of 62 healthy individuals. White blood cell (WBC), neutrophil, lymphocyte, platelet, and monocyte counts obtained retrospectively from complete blood profiles served as the basis for calculating NLR and SII values. In this study, higher WBC, neutrophil counts, NLR, and SII values were observed in schizophrenia and BD patients compared to the control group. In patients with MDD, no significant difference was found in terms of inflammatory blood cell markers compared to healthy controls. Higher NLR and Sİİ values were found in patients with schizophrenia and BD compared to patients with MDD. The results of the study indicate that the significant difference in NLR and SII values persists after treatment in patients with schizophrenia and BD, and that the abnormal inflammatory response continues during the treatment process (Tab. 2, Ref. 41).

Evaluation of Simple Markers of Inflammation and Systemic Immune Inflammation Index in Schizophrenia, Bipolar Disorder Patients and Healthy Controls.

Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), mean platelet volume (MPV), and systemic immune inflammation index (SII) are recently used as indicators of inflammation. NLR, PLR, MLR, and MPV have been evaluated in many studies in patients with schizophrenia and bipolar disorder. However, there are no studies investigating SII. This study aims to evaluate NLR, PLR, MLR, MPV and SII values and complete blood count elements in patients hospitalized with diagnoses of the schizophrenia with psychotic episode and bipolar disorder with manic episode by comparing them with the control group. A total of 149 patients who were hospitalized with the diagnoses of the schizophrenia with psychotic episode and bipolar disorder with manic episode and who met the inclusion criteria were included in our study where the control group was composed of 66 healthy individuals. White blood cell (WBC), neutrophil, lymphocyte, platelet, and monocyte counts were obtained retrospectively from complete blood counts at the time of admission, based on which NLR, PLR, MLR, and SII were calculated. In this study, higher NLR, PLR, and SII values and lower MPV and lymphocyte counts were observed in schizophrenia patients compared to the control group. NLR, PLR, and SII values and neutrophil counts were higher in patients with bipolar disorder compared to the control group. Lower MPV values were found in patients with schizophrenia compared to patients with bipolar disorder. Simple inflammatory and SII values in our study indicate the presence of low-grade systemic inflammation in schizophrenia and bipolar disorder.

Serum Cholinesterase Level as a Marker of Systemic Low-Grade Inflammation in Isolated Systolic Hypertension: A Cross-Sectional Study

Background: Autonomic regulation of local and systemic inflammation through the ‘cholinergic anti-inflammatory pathway’ may have role in persistence of low-grade systemic inflammation in isolated systolic hypertension (ISH). The augmented activity of the enzyme cholinesterase (ChE) leads to degradation of the main anti-inflammatory neurotransmitter ‘acetylcholine’ of this pathway. Despite the role of inflammation in hypertension, serum level of cholinesterase enzyme has not been determined till now in ISH. The study aimed to measure the serum levels of inflammatory marker ChE in comparison to high sensitivity C-reactive protein (hsCRP) to predict the presence of low-grade systemic inflammation and their correlation with blood pressure in ISH patients.
 Methods: A cross-sectional study was conducted in ISH patients (n=30; mean age, 51.00±1.24 years; male/female (M/F) number=18/12). Age and sex matched healthy subjects (n=30, mean age, 51.86±1.40 years; M/F=16/14) were taken as control. Subjects were divided into three groups based on hsCRP levels; group I (healthy: hsCRP≤1.0mg/L), group IIa (patients with mild inflammation: hsCRP≤1.0mg/L), group IIb (patients with moderate to severe inflammation: hsCRP 1.0-10.0mg/L). Overnight fasting blood samples were collected and ChE and hsCRP were assessed using Cholinesterase Liqui-Check and hsCRP turbi-latex diagnostic kits, respectively.
 Results: hsCRP and ChE levels were found significantly high in hypertensive patients than in healthy subjects (p<0.05). In patients at mild stage of inflammation, there was an increase in both ChE and hsCRP, but not linearly as they had no significant correlation with each other. But at moderate to severe inflammation stage, there was a linear rise in both hsCRP and ChE levels. SBP, DBP and PP were significantly correlated with both ChE and hsCRP in patients (p<0.01). Moreover, as the SBP was increased from grade I to II, both hsCRP and ChE levels were also increased.
 Conclusion: Many factors interplay in propagating inflammatory cascade in ISH and all biomarkers of inflammation may not elevate at same point in time and in linear manner. ChE may act as a marker of low-grade systemic inflammation but its comparison must be tested against a standard marker such as hsCRP in large scale studies for finding its true significance in predicting cardiovascular disease risk.

Nonalcoholic fatty liver disease (NAFLD) severity is associated to a nonhemostatic contribution and proinflammatory phenotype of platelets

Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease and ranges from simple steatosis to nonalcoholic steatohepatitis. Recently, a platelet role in NAFLD pathogenesis and progression has been reported in mouse models and in patients. We investigated whether platelets are involved in liver and systemic inflammation processes in NAFLD. In this exploratory study we recruited 24 consecutive patients with biopsy-proven diagnosis of NAFLD and 17 healthy volunteers. We measured plasma levels of inflammatory markers by ELISA. We investigated hemostatic and inflammatory transcripts in circulating platelets and leukocytes from NAFLD patients. We analyzed platelet and neutrophil extracellular traps (NET) accumulations in liver sinusoids using CD42 and H3 citrullinated histones immunohistochemical staining on liver biopsies. NAFLD patients had increased inflammation markers and lipolysaccharides plasma levels. We found significant increase of inflammatory transcripts in circulating platelets and not in leukocytes of NAFLD subjects compared with healthy controls. We demonstrated increased intrahepatic platelet accumulation that correlated with NAFLD activity score (NAS) score and intrahepatic neutrophil extracellular traps (NET) formation in liver biopsies of NAFLD patients. NET formation was higher in livers with higher NAS and inflammation scores. The presence of low-grade systemic inflammation and proinflammatory changes of circulating platelets indicate that platelets participate on systemic inflammatory changes associated with NAFLD. Liver platelet accumulation and liver NET formation, together with low-grade endotoxemia, suggest that platelets may act to protect the liver from invading microorganisms by favoring local NET formation.

Subclinical atherosclerotic vascular disease in chronic obstructive pulmonary disease: Prospective hospital-based case control study.

Introduction:Chronic obstructive pulmonary disease (COPD) is an important non-communicable disease worldwide with a rising global incidence. COPD is associated with multiple co-morbidities. Patients with COPD are at increased risk of atherosclerosis and other cardiovascular events. Cardiovascular diseases are an important cause of morbidity and mortality in COPD. The present case-control study was designed to assess the relationship between sub-clinical atherosclerotic vascular diseases with COPD.Methods:It was a prospective case-control blinded observational study. There were 142 COPD patients and 124 age-and sex-matched controls without COPD and cardiovascular diseases. Frequency of sub-clinical atherosclerosis was assessed by the carotid B-mode duplex ultrasonography assessment of carotid wall intima medial thickness (IMT). Plaque was defined as IMT of more than 1.2 mm.Results:Prevalence of carotid plaqing was significantly higher amongst patients of COPD (38.7%) compared to controls (13.7%, odds ratio 3.9, P < 0.0001). Multinomial logistic regression analysis revealed COPD as an independent predictor of carotid plaqing (r = 0.85, P < 0.023).Conclusion:The frequency of carotid plaqing is high in COPD patients. Carotid plaqing may be due to shared risk factors or the presence of low-grade systemic inflammation. Presence of increased CIMT and carotid plaqing in COPD patients identifies early atherosclerotic changes and future cardiovascular risk. Hence screening of CIMT should be a part of cardiovascular assessment in patients with COPD.

Zinc and Regulation of Inflammatory Cytokines: Implications for Cardiometabolic Disease

In atherosclerosis and diabetes mellitus, the concomitant presence of low-grade systemic inflammation and mild zinc deficiency highlights a role for zinc nutrition in the management of chronic disease. This review aims to evaluate the literature that reports on the interactions of zinc and cytokines. In humans, inflammatory cytokines have been shown both to up- and down-regulate the expression of specific cellular zinc transporters in response to an increased demand for zinc in inflammatory conditions. The acute phase response includes a rapid decline in the plasma zinc concentration as a result of the redistribution of zinc into cellular compartments. Zinc deficiency influences the generation of cytokines, including IL-1β, IL-2, IL-6, and TNF-α, and in response to zinc supplementation plasma cytokines exhibit a dose-dependent response. The mechanism of action may reflect the ability of zinc to either induce or inhibit the activation of NF-κB. Confounders in understanding the zinc-cytokine relationship on the basis of in vitro experimentation include methodological issues such as the cell type and the means of activating cells in culture. Impaired zinc homeostasis and chronic inflammation feature prominently in a number of cardiometabolic diseases. Given the high prevalence of zinc deficiency and chronic disease globally, the interplay of zinc and inflammation warrants further examination.

Elevation of C-Reactive Protein Level Is Associated With Synchronous and Advanced Colorectal Neoplasm in Men

Chronic inflammation has been implicated in the development of colorectal cancer (CRC). The presence of low-grade systemic inflammation, as determined by an elevation of high-sensitivity C-reactive protein (CRP), has been associated with an increased risk of cardiovascular diseases and cancers. However, previous studies of CRP and CRC in cohorts that comprised different genders have yielded conflicting results and little is known about CRP levels in individuals with colorectal adenomas, the precursor lesion of CRC. This study aims to elucidate the association of CRP and colorectal neoplasia. Plasma CRP levels were examined using a cross-sectional design in 6,695 consecutive ethnic Chinese adults who had undergone a complete colonoscopy following a thorough routine health evaluation. Logistic regression analysis was used to correlate the risk of colorectal neoplasia with CRP levels. Plasma CRP levels were significantly higher in subjects with colorectal neoplasia than in those without neoplasia (1.85 mg/L vs 1.55 mg/L, P= 0.04). The presence of synchronous neoplasia, advanced neoplasia, and concurrent synchronous and advanced neoplasia were associated with elevated levels of plasma CRP, after adjustment for other risk factors. Gender stratification revealed a positive association between elevated CRP levels and the risk of colorectal neoplasia in men, but no such corresponding association existed in women. Elevated plasma CRP levels are independently associated with an increased risk of colorectal neoplasia in men, but not in women. These data support the association between chronic inflammation and colorectal neoplasia in men and provide new insights into the underlying mechanisms that warrant further investigation.

Impact of Vitamin D Status and Obesity on C-Reactive Protein in Kidney-Transplant Patients

We examined whether vitamin D status and obesity are associated with low-grade systemic inflammation, as assessed by serum concentrations of C-reactive protein (CRP) in an adult population of kidney-transplant patients. This was a single-center, cross-sectional study. Data were collected between December 2005 and April 2006 from 161 adult (aged >18 years) kidney-transplant patients (mean age, 53.1 years; SD, 11.5 years; females/males, 78/83), with a median kidney-graft age of 7.0 years and serum CRP levels < or =10 mg/L. Vitamin D status was assessed by serum concentrations of 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D). The presence of low-grade systemic inflammation was assessed by serum CRP. Selected lifestyle factors and anthropometric variables were determined in a subgroup of patients (n = 90). Bivariate correlation and multiple regression analyses were performed. Hypovitaminosis D (ie, S-25-OHD < or =75 nmol/L) was present in 73% of females, and 89% of males. The median level of serum CRP was 1.7 mg/L. Vitamin D status was not significantly associated with serum CRP. In the patient subgroup, indices of obesity (body mass index, body weight, and fat mass) correlated positively, and lean body mass correlated negatively, with serum CRP. Only fat mass remained significantly associated with serum CRP in multiple regression analysis. No impact of vitamin D status on low-grade systemic inflammation was found. Fat mass correlated positively with CRP, suggesting that obesity may increase the risk of cardiovascular disease and chronic allograft rejection in kidney-transplant patients.

Body fat and circulating leukocytes in children

To determine the effects of obesity on baseline levels of circulating granulocytes, monocytes, and lymphocyte subtypes in otherwise healthy children. Two group comparison of leukocytes in normal weight control and overweight children. In total, 38 boys and girls, ages 6-18 years, divided in two groups: normal weight, (NW, BMI<85th %tile, n=15) and overweight (OW, body mass index (BMI)>85th %tile, n=23). BMI obtained from direct measures of height and body mass. Body fat was assessed by DEXA. Complete blood counts (CBC) were obtained by standard clinical hematology methods and surface antigen staining by flow cytometry. The OW group compared to the NW group had increased total leukocytes counts (P=0.011), neutrophils (P=0.006), monocytes (P=0.008), total T (CD3) lymphocytes (P=0.022), and Helper T (CD4(+)) cells (P=0.003). Significant correlations were evident between leukocytes, and BMI percentile, BMI, or percent body fat. Neither lean body mass nor VO(2peak) per unit lean body mass were significantly related to any of the leukocytes. Percent body fat and BMI percentile were positively correlated (P<0.05) to total T cells (CD3) and/or helper T cells (CD4(+)). A group of 23 overweight children displayed elevated counts in most types of circulating immune cells, suggesting the presence of low-grade systemic inflammation, a known pathogenetic mechanism underlying most long-term complications of obesity. Our data provide an additional rationale for the importance of avoiding or correcting pediatric obesity.

Association between depression and elevated C-reactive protein.

Depression has been related to a higher risk of developing coronary heart disease, but the mechanism that accounts for this association is unclear. Because atherosclerosis is an inflammatory process, depression could increase the risk of coronary heart disease by inducing or promoting inflammation. The objective of the present study was to investigate the association between history of major depressive episode and presence of low-grade systemic inflammation as measured by serum C-reactive protein (CRP). We analyzed data from the Third National Health and Nutrition Examination Survey, a representative sample of the US population from 1988 to 1994. Participants included a total of 6149 individuals aged 17 to 39 years who were free of cardiovascular diseases and chronic inflammatory conditions. The main predictor variable of interest was lifetime history of a major depressive episode as assessed by means of the Diagnostic Interview Schedule. The main outcome variable was the presence or absence of an elevated CRP level (> or =22 mg/dl). Among men, history of a major depressive episode was associated with elevated CRP, particularly for recent episodes (up to 6 months before assessment). In multivariate analyses, men with a history of major depressive episode had 2.77 times higher odds of elevated CRP compared with never-depressed men (95% confidence interval, 1.43-5.26). The adjusted odds ratio was 3.81, 3.98, 1.51, and 1.52 for men who had their last major depressive episode less than 1 month before, 1 to 6 months before, 7 to 12 months before, and more than 12 months before assessment, respectively (p for trend =.004). In women, a comparable association between depression and CRP was quite weak and not significant. A recent history of major depressive episode is strongly associated with elevated CRP in men aged 17 to 39. In this group, low-grade systemic inflammation could represent a mechanism linking depression to cardiovascular risk.