Baseline Levels Of Inflammatory Markers Research Articles

The significance of inflammatory markers in prognosticating the effectiveness and safety of immunotherapy in conjunction with chemotherapy during the primary intervention of advanced non-small cell lung carcinoma

ObjectiveThe aim of this study is to scrutinize the prognostic significance of inflammatory biomarkers concerning the effectiveness and safety of combining PD-1 inhibition with chemotherapy in the management of advanced NSCLC. MethodsWe conducted a retrospective analysis involving 206 NSCLC patients who received treatment at Qingdao Municipal Hospital. The study encompassed the acquisition of baseline clinical attributes and hematological parameters of these patients. The optimal threshold values for PLT and NLR were ascertained based on pre-treatment evaluations, with a particular focus on their association with PFS. Variables linked to PFS were subject to scrutiny through Kaplan-Meier analysis and logistic regression. The Receiver Operating Characteristic (ROC) curve served as the means to determine the ideal cut-off values for categorizing levels of inflammatory markers into high and low classifications. We employed Chi-square tests to evaluate the relationship between elevated and reduced baseline levels of inflammatory markers and irAE. ResultsKaplan-Meier analysis disclosed that patients in the low baseline PLT group and the low NLR group exhibited a substantially more favorable prognosis in contrast to their counterparts in the high baseline PLT and high NLR groups. Multivariate analysis indicated that diminished baseline PLT and NLR levels before treatment independently foretell extended PFS. Chi-square analysis underscored a substantial correlation between baseline WBC, NEUT, LYMPH, MONO, and NLR levels and irAE. ConclusionSubdued baseline PLT and NLR levels may serve as indicators of a more auspicious prognosis in patients contending with advanced NSCLC undergoing the combination of PD-1 inhibition and chemotherapy. Elevated baseline levels of inflammatory markers antedating PD-1 therapy in advanced NSCLC may be intimately interrelated with the occurrence of irAE.

Characteristics of Inflammatory Markers in Diabetic Foot Patients and Their Relationship With Prognosis of Diabetic Foot Ulcers

To explore the characteristics of baseline inflammatory markers in diabetic foot patients and their relationship with the prognosis of diabetic foot ulcers. The clinical data of diabetic foot patients (n=495) admitted to West China Hospital, Sichuan University since 2016 were retrospectively collected through the hospital electronic medical record system to analyze the characteristics of inflammatory markers and their relationship with the prognosis of diabetic foot ulcers. White blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) levels were significantly higher in patients defined as grade 4 on the Wagner Scale than those in patients defined as grade 0-3 on the Wagner Scale. Neutrophil percentage (NE%) was higher in Wagner grade-4 patients than those in Wagner grade-0 and grade-1 patients and higher in Wagner grade-3 patients than those in Wagner grade-0 patients. NE%, CRP, PCT, and IL-6 levels were positively correlated with the severity of diabetic foot, with the respective odds ratio (OR) at 95% confidence interval (CI) being 1.038 (1.019-1.056), 1.019 (1.012-1.026), 8.225 (2.015-33.576), and 1.017 (1.008-1.025). Using Wagner grade-0 patients as the reference, patients with higher WBC were more likely to progress to Wagner grade 2, 3, and 4, with the respective OR (95% CI) values being 1.260 (1.096-1.447), 1.188 (1.041-1.356), and 1.301 (1.137-1.490); patients with higher ESR were more likely to progress to Wagner grade 3 and 4, with the respective OR (95% CI) values being 1.030 (1.006-1.054) and 1.045 (1.019-1.071). Baseline ESR (P=0.008), CRP (P=0.039), and IL-6 (P=0.033) levels were lower in patients who had received antibiotics prior to their admission than those in patients who had not received antibiotics before admission. The levels of WBC, NE%, ESR, PCT, and IL-6 were lower in the full recovery group than those in the group of patients who did not respond to treatment. The higher the levels of NE% and IL-6, the worse the prognosis of diabetic foot ulcers became, with the respective OR (95% CI) values being 1.030 (1.010-1.051) and 1.008 (1.002-1.013). The severity of diabetic foot ulcers increased with the rise in baseline levels of inflammatory markers. Elevated baseline NE% and IL-6 levels suggest a poor prognosis. Our findings suggest that early assessment of diabetic foot infection and standardized antibiotic therapy should be implemented to improve the prognosis.

Longitudinal study of inflammation and relapse in schizophrenia

IntroductionThe clinical course of schizophrenia is often characterized by recurrent relapses. Blood inflammatory markers are altered in acute psychosis, and may be state markers for illness relapse in schizophrenia. Few studies have investigated longitudinal, intra-individual changes in inflammatory markers as a predictor of relapse. In the present study, we explored this association in a relapse prevention trial in patients with schizophrenia. MethodsWe analyzed blood inflammatory markers in 200 subjects, with a mean 11 samples per subject, during the 30 month Preventing Relapse in schizophrenia: Oral Antipsychotics Compared to Injectable: eValuating Efficacy (PROACTIVE) trial. Associations between longitudinal changes in inflammatory markers and relapse were analyzed using a within-subjects design. Results70 (35 %) of subjects relapsed during the study period. There were no significant differences in mean inflammatory marker levels based on relapse status (yes/no). Baseline levels of inflammatory markers did not predict incident relapse. Among subjects who relapsed, there was a significant decrease in mean blood IL-6 (n = 38, p = 0.019) and IFN-γ (n = 44, p = 0.012) levels from the visit before the relapse to the visit after relapse. ConclusionAlthough there was some evidence for inflammation as a potential state marker for acute psychosis, we did not find significant evidence for its utility as a relapse-predictive marker.

Higher baseline inflammatory marker levels predict greater cognitive decline in older people with type 2 diabetes: year 10 follow-up of the Edinburgh Type 2 Diabetes Study

Aims/hypothesisWe aimed to determine the longitudinal association of circulating markers of systemic inflammation with subsequent long-term cognitive change in older people with type 2 diabetes.MethodsThe Edinburgh Type 2 Diabetes Study is a prospective cohort study of 1066 adults aged 60 to 75 years with type 2 diabetes. Baseline data included C-reactive protein, IL-6, TNF-α fibrinogen and neuropsychological testing on major cognitive domains. Cognitive testing was repeated after 10 years in 581 participants. A general cognitive ability score was derived from the battery of seven individual cognitive tests using principal component analysis. Linear regression was used to determine longitudinal associations between baseline inflammatory markers and cognitive outcomes at follow-up, with baseline cognitive test results included as covariables to model cognitive change over time.ResultsFollowing adjustment for age, sex and baseline general cognitive ability, higher baseline fibrinogen and IL-6 were associated with greater decline in general cognitive ability (standardised βs = −0.059, p=0.032 and −0.064, p=0.018, respectively). These associations lost statistical significance after adjustment for baseline vascular and diabetes-related covariables. When assessing associations with individual cognitive tests, higher IL-6 was associated with greater decline in tests of executive function and abstract reasoning (standardised βs = 0.095, p=0.006 and −0.127, p=0.001, respectively). Similarly, raised fibrinogen and C-reactive protein levels were associated with greater decline in processing speed (standardised βs = −0.115, p=0.001 and −0.111, p=0.001, respectively). These associations remained statistically significant after adjustment for the diabetes- and vascular-related risk factors.Conclusions/interpretationHigher baseline levels of inflammatory markers, including plasma IL-6, fibrinogen and C-reactive protein, were associated with subsequent cognitive decline in older people with type 2 diabetes. At least some of this association appeared to be specific to certain cognitive domains and to be independent of vascular and diabetes-related risk factors.Graphical abstract

Distinctive Role of the Systemic Inflammatory Profile in Non-Small-Cell Lung Cancer Younger and Elderly Patients Treated with a PD-1 Immune Checkpoint Blockade: A Real-World Retrospective Multi-Institutional Analysis.

An immune checkpoint blockade with mAbs to PD-1 and PD-L1 is an expanding therapeutic option for mNSCLC patients. This treatment strategy is based on the use of mAbs able to restore the anti-tumor activity of intratumoral T cells inhibited by PD-1 binding to PD-L1/2 on tumor and inflammatory cells. It has been speculated that a chronic status of systemic inflammation as well as the immunosenescence physiologically occurring in elderly patients may affect the efficacy of the treatment and the occurrence of irAEs. We performed a multi-institutional retrospective study aimed at evaluating the effects of these mAbs (nivolumab or atezolizumab) in 117 mNSCLC patients younger (90 cases) and older (27 cases) than 75 years in correlation with multiple inflammatory parameters (NLR, CRP, ESR, LDH and PCT). No differences were observed when the cohorts were compared in terms of the frequency of PFS, OS, inflammatory markers and immune-related adverse events (irAEs). Similarly, the occurrence of irAEs was strictly correlated with a prolonged OS survival in both groups. On the contrary, a negative correlation between the high baseline levels of inflammatory markers and OS could be demonstrated in the younger cohort only. Overall, PD-1/PD-L1-blocking mAbs were equally effective in young and elderly mNSCLC patients; however, the detrimental influence of a systemic inflammation at the baseline was only observed in young patients, suggesting different aging-related inflammation immunoregulative effects.

Effects of Acute Fructose Loading on Markers of Inflammation-A Pilot Study.

Inflammation plays a role in development of diabetic complications. The postprandial state has been linked to chronic low grade inflammation. We therefore aimed to investigate the acute effects of fructose loading, with and without a pizza, on metabolic and inflammatory markers in patients with type 2 diabetes (T2D) (n = 7) and in healthy subjects (HS) (n = 6), age 47–76 years. Drinks consumed were blueberry drink (18 g fructose), Coca-Cola (17.5 g fructose), and fructose drink (35 g fructose). The levels of glucose, insulin, insulin-like growth factor binding protein-1 (IGFBP-1) and inflammatory markers: Interleukin-6 (IL-6), Monocyte chemoattractant protein-1 (MCP-1), Interleukin-18 (IL-18), Intercellular Adhesion Molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and bacterial lipopolysaccharides (LPS) were analyzed in blood. The postprandial responses were assessed using Wilcoxon’s matched-pairs test, Friedman’s ANOVA and Mann–Whitney U test. There was no difference in baseline levels of inflammatory markers between the groups. In T2D, MCP-1 decreased following blueberry drink and Coca-Cola (p = 0.02), Coca-Cola + pizza and fructose + pizza (p = 0.03). In HS, IL-6 increased following blueberry + pizza and fructose + pizza (p = 0.03), there was a decrease in MCP-1 following blueberry drink and Coca-Cola (p = 0.03), and in ICAM-1 following blueberry + pizza (p = 0.03). These results may indicate a role for MCP-1 as a link between postprandial state and diabetes complications, however further mechanistic studies on larger population of patients with T2D are needed for confirmation of these results.

Assessment of neuroinflammation in the aging hippocampus using large-molecule microdialysis: Sex differences and role of purinergic receptors

Aging is associated with an enhanced neuroinflammatory response to acute immune challenge, often termed “inflammaging.” However, there are conflicting reports about whether baseline levels of inflammatory markers are elevated under ambient conditions in the aging brain, or whether such changes are observed predominantly in response to acute challenge. The present studies utilized two distinct approaches to assess inflammatory markers in young and aging Fischer 344 rats. Experiment 1 examined total tissue content of inflammatory markers from hippocampus of adult (3 month), middle-aged (12 month), and aging (18 month) male Fischer (F) 344 rats using multiplex analysis (23-plex). Though trends emerged for several cytokines, no significant differences in basal tissue content were observed across the 3 ages examined. Experiment 2 measured extracellular concentrations of inflammatory factors in the hippocampus from adult (3 month) and aging (18 month) males and females using large-molecule in vivo microdialysis. Although few significant aging-related changes were observed, robust sex differences were observed in extracellular concentrations of CCL3, CCL20, and IL-1α. Experiment 2 also evaluated the involvement of the P2X7 purinergic receptor in neuroinflammation using reverse dialysis of the selective agonist BzATP. BzATP produced an increase in IL-1α and IL-1β release and rapidly suppressed the release of CXCL1, CCL2, CCL3, CCL20, and IL-6. Other noteworthy sex by aging trends were observed in CCL3, IL-1β, and IL-6. Together, these findings provide important new insight into late-aging and sex differences in neuroinflammation, and their regulation by the P2X7 receptor.

Influence of Weight Reduction and Enhanced Protein Intake on Biomarkers of Inflammation in Older Adults with Obesity

Both aging and obesity are associated with increased levels of pro-inflammatory metabolites, while weight reduction is associated with improvements in inflammatory status. However, few studies have explored the response of key inflammatory markers to the combined settings of weight reduction in an aging population. There are also few studies that have investigated the potential impact of diet composition on inflammatory marker responses. In the MEASUR-UP trial, we evaluated changes in baseline levels of inflammatory markers with post-study levels for a traditional weight loss control group versus a group with generous, balanced protein intake. In this 6-month randomized controlled trial (RCT), older (≥60 years) adults with obesity (BMI ≥30 kg/m2) and Short Physical Performance Battery (SPPB) score of 4–10 were randomly assigned to either a traditional weight loss regimen, (Control, n = 14) or one with higher protein intake (≥30 g) at each meal (Protein, n = 25). All participants were prescribed a hypo-caloric diet and attended weekly support and education groups and weigh-ins. Protein participants consumed ≥30 g of high-quality protein/meal, including lean and extra lean beef provided to them for two of the three meals per day. Protein intakes were 0.8 and 1.2 g/kg/day for Control and Protein, respectively. Adiponectin, leptin, C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6, IL-8, serum amyloid A (SAA), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and glycated serum protein (GSP) levels were measured at 0 and 6-month time points. At the 6-month endpoint, there was significant weight loss and decrease in BMI in both the Control (−4.8 ± 8.2 kg; −2.3 ± 2.4 kg/m2; p = 0.05) and Protein (−8.7 ± 7.4 kg; −2.9 ± 2.3 kg/m2; p < 0.0001) groups. SPPB scores improved in both arms, with a superior functional response in Protein (p < 0.05). Body fat (%) at baseline was positively correlated with leptin, hs-CRP, VCAM-1, ICAM-1, and GSP. Several markers of inflammation responded to the Protein group: leptin (p < 0.001), hs-CRP (p < 0.01), and ICAM-1 (p < 0.01) were decreased and adiponectin increased (p < 0.01). There were no significant changes in any inflammatory markers in the Control arm. In the between group comparison, only adiponectin trended towards a group difference (more improvement in Protein; p < 0.07). Our findings in the MEASUR-UP trial show that a weight loss diet with enhanced protein intake is comparable to an adequate protein diet in terms of weight loss success and that it can lead to improvements in inflammatory status, specifically for adiponectin, leptin, hs-CRP, and ICAM-1. These findings are important given current recommendations for higher protein intakes in older adults and justify the additional study of the inflammatory impact of an enhanced protein diet. (ClinicalTrials.gov identifier: NCT01715753)Trial registration: ClinicalTrials.gov identifier: NCT01715753.

Antioxidants from diet or supplements do not alter inflammatory markers in adults with cardiovascular disease risk. A pilot randomized controlled trial

Antioxidants have been reported to have anti-inflammatory effects, but there is a lack of research comparing food to supplement antioxidant sources. The aim of this study was to determine if increases in intake of foods naturally rich in antioxidants would lower blood levels of inflammatory markers more than consuming antioxidant supplements among adults with cardiovascular disease risk factors. Eighty-eight generally healthy adults with ≥1 elevated risk factor for cardiovascular disease were randomized in a single-blind (diets)/double-blind (supplements), parallel-group study for 8 weeks. Participants consumed (1) usual diet and placebo pills (n = 29), (2) usual diet and antioxidant supplements (n = 29), or (3) antioxidant-rich foods closely matched to antioxidant content of supplements and placebo (n = 30). Usual diet combined with antioxidant supplements or increased antioxidant-rich food intake was designed to approximately double daily habitual antioxidant intake. Antioxidant pills included carotenoids, mixed tocopherols, vitamin C, and selenium. Fasting blood samples were analyzed for inflammatory marker concentrations of interleukin-6, monocyte chemotactic protein-1, and soluble intercellular adhesion molecule-1. Participants in the intervention groups successfully doubled most antioxidants as verified by diet records and elevated blood concentrations in treatment groups. Baseline levels of inflammatory markers for the entire study group were 110 ± 65 pg/mL for monocyte chemotactic protein-1, 0.9 ± 0.7 pg/mL for interleukin-6, and 217 ± 56 ng/mL for soluble intercellular adhesion molecule-1 (means ± standard deviation) and did not differ by treatment arm. After 8 weeks, there were no significant within-group changes or between-group 8-week change differences in inflammatory marker concentrations. In conclusion, no beneficial effects were detected on the inflammatory markers investigated in response to antioxidants from foods or supplements.

Marcadores inflamatórios como fatores preditivos para o efeito antidepressivo dos inibidores seletivos da recaptura de serotonina (ISRS)

A influência da inflamação na fisiopatologia da depressão e o papel da depressão no desenvolvimento de um estado pró-inflamatório têm sido apoiados por diversos estudos. O transtorno depressivo maior (TDM), principal diagnóstico de depressão, tem os inibidores seletivos da recaptação de serotonina (ISRS) como tratamento farmacológico de primeira linha. Esforços têm sido feitos para identificar fatores preditivos da responsividade ao tratamento antidepressivo os ISRS. Portanto, esta revisão tem como objetivo avaliar a hipótese de que níveis basais de marcadores inflamatórios predizem a responsividade do TDM ao tratamento com ISRS. Métodos: Pesquisamos o banco de dados PubMed, incluindo as palavras-chave (“ISRS” ou “sertralina” ou “citalopram” ou “fluvoxamina” ou “escitalopram” ou “fluoxetina” ou “paroxetina”) e (“citocinas” ou “CRP” ou “TNF” ou “inflamatório”) e (“transtorno depressivo maior” ou “depressão maior”). Resultados: A pesquisa identificou 245 manuscritos, dos quais 12 satisfizeram os critérios de inclusão e exclusão e foram incluídos nesta revisão. A análise destes manuscritos sugeriu que níveis elevados de interleucina 6 (IL-6), interleucina 1β (IL-1β), fator de necrose tumoral – alfa (TNF-α) e proteína C-reativa (PCR) na avaliação basal podem prever baixa responsividade da depressão ao tratamento com ISRS. Fatores de confusão como deficiência cognitiva, cronicidade e gravidade da depressão, subtipo melancólico, idade e sexo, não foram sistematicamente incluídos nos estudos. Conclusão: Os achados desta revisão sugerem que níveis elevados de marcadores pró-inflamatórios na avaliação basal podem predizer baixa responsividade do TDM ao tratamento com ISRS. Estudos com controle adequado para fatores de confusão são necessários.

Influence of Genetic Variations on Levels of Inflammatory Markers of Healthy Subjects at Baseline and One Week after Clopidogrel Therapy; Results of a Preliminary Study

We aimed to assess the association between the most common polymorphisms of cytochrome P450 (CYP) epoxygenases on the plasma levels of inflammatory markers in a population of healthy subjects. We also sought to determine whether CYP2C19*2 polymorphism is associated with the anti-inflammatory response to clopidogrel. In a population of 49 healthy young males, the baseline plasma levels of inflammatory markers including C-reactive protein, haptoglobin, orosomucoid acid, CD-40 were compared in carriers vs. non-carriers of the most frequent CYP epoxygenase polymorphisms: CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C8*2 and CYP2J2*7. Also, the variation of inflammatory markers from baseline to 7 days after administration of 75 mg per day of clopidogrel were compared in carriers vs. non-carriers of CYP2C19* allele and also in responders vs. hypo-responders to clopidogrel, determined by platelet reactivity tests. There was no significant association between epoxygenase polymorphisms and the baseline levels of inflammatory markers. Likewise, CYP2C19* allele was not associated with anti-inflammatory response to clopidogrel. Our findings did not support the notion that the genetic variations of CYP epoxygenases are associated with the level of inflammatory markers. Moreover, our results did not support the hypothesis that CYP2C19*2 polymorphism is associated with the variability in response to the anti-inflammatory properties of clopidogrel.

Race and gender variation in response to evoked inflammation

BackgroundRace- and gender-variation in innate immunity may contribute to demographic differences in inflammatory and cardiometabolic disease; yet their influence on dynamic responses during inflammatory stress is poorly understood. Our objective was to examine race and gender influence on the response to experimental endotoxemia.MethodsThe Genetics of Evoked Responses to Niacin and Endotoxemia (GENE) study was designed to investigate regulation of inflammatory and metabolic responses during low-grade endotoxemia (LPS 1 ng/kg intravenously) in healthy individuals (median age 24, IQR=7) of European (EA; n=193, 47% female) and African ancestry (AA; n=101, 59% female).ResultsBaseline clinical, metabolic, and inflammatory biomarkers by race and gender were consistent with epidemiological literature; pre-LPS cytokines (e.g. median (IQR) IL-6, 2.7 (2) vs.2.1 (2) pg/ml, P=0.001) were higher in AA than EA. In contrast, acute cytokine responses during endotoxemia were lower in AA than EA (e.g. median (IQR) peak IL-1RA, 30 (38) vs.43 (45) ng/ml P=0.002) as was the induction of hepatic acute-phase proteins (e.g. median (IQR) peak CRP 12.9 (9) vs.17.4 (12) mg/L P=0.005). Further, baseline levels of cytokines were only weakly correlated with peak inflammatory responses (all rs <0.2) both in AA and in EA. There were less pronounced and less consistent differences in the response by gender, with males having a higher AUC for CRP response compared to females (median (IQR) AUC: 185 (112) vs. 155 (118), P=0.02).ConclusionsWe observed lower levels of evoked inflammation in response to endotoxin in AA compared with EA, despite similar or higher baseline levels of inflammatory markers in AA. Our data also suggest that levels of inflammatory biomarkers measured in epidemiological settings might not predict the degree of acute stress-response or risk of diseases characterized by activation of innate immunity.Trial registrationFDA clinicaltrials.gov registration number NCT00953667

Baseline NT-proBNP and biomarkers of inflammation and necrosis in patients with ST-segment elevation myocardial infarction: insights from the APEX-AMI trial

Coronary plaque rupture is associated with a systemic inflammatory response. The relationship between baseline N-terminal pro B-type natriuretic peptide (NT-proBNP), a prognostic marker in patients with acute coronary syndromes, and systemic inflammatory mediators in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) is not well described. Of 5,745 STEMI patients treated with primary PCI in the APEX-AMI trial, we evaluated the relationship between baseline NT-proBNP levels and baseline levels of inflammatory markers and markers of myonecrosis in a subset of 772 who were enrolled in a biomarker substudy. Spearman correlations (r (s)) were calculated between baseline NT-proBNP levels and a panel of ten systemic inflammatory biomarkers. Interleukin (IL)-6, a pro-inflammatory cytokine, was significantly positively correlated with NT-proBNP (r (s) = 0.317, P < 0.001). In a sensitivity analysis excluding all heart failure patients, the correlation between baseline IL-6 and NT-proBNP remained significant (n = 651, r (s) = 0.296, P < 0.001). A positive association was also observed with high sensitivity C-reactive protein (r (s) = 0.377, P < 0.001) and there was a weak negative correlation with the anti-inflammatory cytokine IL-10 (r (s) = -0.109, P = 0.003). No other significant correlations were observed among the other testes inflammatory cytokines and chemokines. In STEMI patients undergoing primary PCI, the pro-inflammatory cytokine IL-6 was modestly correlated with baseline NT-proBNP levels. This relationship remained significant in patients without heart failure. This finding is consistent with pre-clinical and clinical research suggesting that systemic inflammation may influence NT-proBNP expression independently of myocardial stretch.

Markers of inflammation in prevalent and incident Parkinson’s disease in the Cardiovascular Health Study

BackgroundStudies demonstrate existence of inflammation in prevalent Parkinson’s disease (PD). We assessed associations of baseline levels of inflammatory markers with prevalent PD at baseline (1989) and incident PD identified over 13 years of follow-up of the Cardiovascular Health Study. MethodsBlood samples at baseline were measured for fibrinogen, interleukin-6, tumor necrosis factor-α, C-reactive protein, albumin, and white blood cells. The analysis included 60 prevalent and 154 incident PD cases. ResultsRisk of prevalent PD was significantly higher per doubling of IL-6 among women (odds ratio [OR]=1.5, 95% confidence interval [CI]: 1.0, 2.4) and WBC among men (OR: 2.4, 95% CI: 1.2, 4.9) in multivariate models. Risk of incident PD was not associated with higher levels of any biomarker after adjusting for age, smoking, African American race, and history of diabetes. Inverse associations with incident PD were observed per doubling of C-reactive protein (OR=0.9; 95% CI: 0.8, 1.0) and of fibrinogen among women (OR=0.4; 95% CI: 0.2, 0.8). ConclusionsAlthough inflammation exists in PD, it may not represent an etiologic factor. Our findings suggest the need for larger studies that measure inflammatory markers before PD onset.

Erythrocyte sedimentation rate, C‐reactive protein level, and serum amyloid A protein for patient selection and monitoring of anti–tumor necrosis factor treatment in ankylosing spondylitis

To study the usefulness of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum amyloid A (SAA) for response prediction and monitoring of anti-tumor necrosis factor (anti-TNF) treatment in ankylosing spondylitis (AS) patients. Patients were included consecutively before starting etanercept or infliximab treatment. ASsessment in Ankylosing Spondylitis (ASAS) response, defined as a 50% improvement or an absolute improvement of 2 points of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; 0-10 scale), was assessed at 3 months. Inflammatory markers and the BASDAI were collected at baseline and 1 and 3 months. Longitudinal data analysis was performed to compare associations between inflammatory markers and the BASDAI over time by calculating standardized betas. Predictive values of baseline levels of inflammatory markers for ASAS response were calculated. In total, 155 patients were included, of whom, after 3 months of treatment, 70% in the etanercept cohort and 71% in the infliximab cohort responded. All markers, notably SAA, decreased significantly (P < 0.0001). Standardized betas were 0.49 for ESR, 0.43 for CRP, and 0.39 for SAA. Normal baseline levels of CRP and SAA were significantly associated with nonresponse. A combination of elevated CRP and SAA levels at baseline revealed the highest predictive value (81%) for ASAS response. ESR, CRP, and SAA were significantly associated with the BASDAI over 3 months, and the association with ESR was the strongest. Elevated baseline CRP and SAA levels revealed the highest predictive value for response. Together, this study demonstrates that inflammatory markers, and notably CRP and SAA, may facilitate patient selection and monitoring of efficacy of anti-TNF treatment in AS, and could be added to response criteria.

Serum levels of interleukin‑6, interleukin‑10 and C‑reactive protein in patients with myocardial infarction treated with primary angioplasty during a 6‑month follow‑up

Recent studies indicate that inflammatory and immune factors are involved in the post-infarction cardiac remodeling. We evaluated serum levels of interleukin-6 (IL-6), interleukin-10 (IL-10) and C-reactive protein (CRP) in patients with acute coronary syndrome with ST-segment elevation myocardial infarction (STEMI) in the acute phase of the disease and 6 months later. Moreover we sought to determine the effect of selected clinical parameters on the levels of the inflammatory factors. The study involved 75 patients with STEMI, aged 36-82 years, treated with primary angioplasty. Blood samples for determination of IL-6, IL-10 and CRP levels were taken on the 3rd and 7th day of hospitalization and after 6 months. In the acute phase of myocardial infarction (MI) the levels of IL-6, IL-10 and CRP, as well as the IL-6/IL-10 and CRP/IL-10 indexes were higher than in the control group. Six months later the CRP level decreased significantly, and the levels of IL-6 and IL-10 and the studied indices normalized. In the acute phase of MI there were positive correlations between the studied factors. The independent predictors of IL-6, IL-10 and CRP levels were body mass index (BMI), troponin I, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and the baseline levels of inflammatory markers. In the acute phase of MI, inflammatory activation is enhanced with predominant proinflammatory response. In the course of the healing process within 6 months inflammation is suppressed and the balance between pro- and anti-inflammatory activation is restored. The size of MI, BMI, lipid levels and the baseline levels of inflammatory markers influence the levels of inflammatory factors.

Tomato-rich (Mediterranean) diet does not modify inflammatory markers

The Mediterranean diet is rich in lycopene and has been reported to reduce cardiovascular events. The mechanism of prevention of cardiovascular events has not been clearly established. Our aim was to study the effects of a tomatoes-rich diet on markers of vascular inflammation. Plasma concentrations of E-selectin, intercellular adhesion molecule 1 (ICAM-1), and high sensitivity C-reactive protein (hs-CRP) were determined by ELISA in 103 apparently healthy volunteers. Volunteers were randomly assigned to two groups: 50 participants ate 300 g tomatoes daily for 1 month, and 53 participants ate their usual diet with tomatoes prohibited during that period. Markers of inflammation were measured before enrollment and 1 month after their assigned diet. The two diet groups had similar baseline clinical characteristics and similar baseline levels of inflammatory markers. After 30 days of assigned diet concentrations of hs-CRP, E-selectin and ICAM-1 were unchanged compared with baseline in the tomato-rich diet. However, ICAM-1 concentration was increased in the regular diet group from 247.55+/-55 ng/ml to 264.71+/-60.42 ng/ml (P=0.01). The mechanisms of benefit of the tomato-rich diet are not directly related to inhibition of markers of vascular inflammation.

D‐Dimer and Inflammatory Markers as Predictors of Functional Decline in Men and Women with and without Peripheral Arterial Disease

To determine whether higher circulating levels of inflammatory and thrombotic markers are associated with greater decline in lower extremity performance. Prospective cohort. Academic medical center. Three hundred thirty-seven men and women with lower extremity peripheral arterial disease (PAD) and 215 without PAD. Objective measures of leg function, including the 6-minute walk and Short Physical Performance Battery (SPPB), were obtained at baseline and annually for 3 years. D-dimer, high-sensitivity C-reactive protein, serum amyloid A, and fibrinogen levels were measured at baseline. Participants were categorized into one of three groups, ranging from low to high levels of inflammation, depending on the number of individual blood factors in the lowest and highest tertiles for each corresponding blood factor. Adjusting for age, sex, race, ankle brachial index, comorbidities, and other confounders, greater inflammation was associated with greater decline in the SPPB (P=.008). Results were similar when repeated in participants with and without PAD separately (P for trend=.04 for participants with PAD and .07 for participants without PAD). In fully adjusted analyses, there were no significant associations between inflammation group and decline in 6-minute walk performance. Higher baseline levels of inflammatory markers and D-dimer were associated with greater decline in the SPPB at 3-year follow-up in persons with and without PAD.

Cartilage biomarkers in ankylosing spondylitis: Relationship to clinical variables and treatment response

Ankylosing spondylitis (AS) is a progressive disease in which chronic inflammation can lead to extensive new bone formation throughout the spine. At present, few measures of the activity or extent of the disease are available. In this study, we sought to determine whether markers of cartilage synthesis and degradation could provide such quantitative measures. Serum samples from 23 patients receiving infliximab treatment for AS were obtained at baseline and at weeks 2, 6, 14, and 22. Patients were stratified with respect to joint involvement and baseline levels of inflammatory markers, and responders were defined according to the Assessments in Ankylosing Spondylitis 20% criteria. Serial measurements of interferon-gamma, tumor necrosis factor alpha, transforming growth factor beta (TGFbeta), interleukin-10 (IL-10), and IL-1 were done at each time point. The following biomarkers were measured by enzyme-linked immunosorbent assay: the proteoglycan aggrecan 846 epitope, a marker of cartilage turnover; C-propeptide of type II collagen (CPII), a biosynthesis marker; and the Col2-3/4(long mono) (C2C) and Col2-3/4(short) (C1-2C) neoepitopes, reflecting collagen cleavage of type II collagen and type I/type II collagen, respectively. At baseline, patients with AS demonstrated significant elevations in serum levels of CPII, the 846 epitope, and the CPII-to-C2C (CPII:C2C) ratio (but not C2C or C1-2C) compared with normal controls. Of the biomarkers examined, only CPII:C2C showed a correlation with the C-reactive protein (CRP) level. Among the biomarker-cytokine relationships, TGFbeta demonstrated a trend toward a positive correlation with the 846 epitope. In AS, elevated serum levels of CPII and the 846 epitope may be related to biosynthetic turnover of hyaline cartilage and the intervertebral discs but may also reflect progressive bone formation as a result of endochondral ossification. The correlation of the CPII:C2C ratio with CRP suggests that the CPII:C2C ratio might prove to be a useful marker of disease activity in AS.

Effect of preexisting statin use on expression of C-reactive protein, adhesion molecules, interleukin-6, and antioxidized low-density lipoprotein antibody in patients with unstable angina undergoing coronary stenting

Statins are believed to reduce coronary heart disease by mechanisms in addition to their well-known cholesterol lowering effect. We studied the effect of statins on expression of C-reactive protein (CRP), interleukin-6 (IL-6), adhesion molecules, and antioxidized low-density lipoprotein antibody (anti-oxLDL Ab) in patients with unstable angina (Braunwald class IIb or IIIb) undergoing coronary stenting. Consecutive 50 patients with unstable angina were included in the study. We classified the study subjects as patients using statins (Group A, n=20, men 10, mean age 62 years) and patients not using statins (Group B, n=30, men 15, mean age 60 years). Baseline levels of inflammatory markers were similar in the two groups. However, 24 h after coronary stenting, serum levels of CRP (2.00 vs. 4.63 mg/l, p < 0.05), intercellular adhesion molecule-1 (ICAM-1) (217 vs. 261 ng/ml, p < 0.01), and anti-oxLDL Ab (8.97 vs. 12.96 U/ml, p < 0.05) were significantly higher in Group B than in Group A. Furthermore, 72 h after coronary stenting, serum levels of CRP (3.00 vs. 5.50 mg/l, p < 0.01) and ICAM-1 (222 vs. 277 ng/ml, p < 0.05) were significantly higher in Group B than in Group A. Preexisting statin therapy plays a role in reducing the serum levels of CRP, ICAM-1, and anti-oxLDL Ab after coronary stenting in patients with unstable angina. These data support an anti-inflammatory or plaque-stabilizing effect of statin therapy.