Showing papers on "C-reactive protein published in 2005"

Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial

Abstract: Background and aims: Ulcerative colitis (UC) is an acute and chronic inflammatory disease of the large bowel with unknown aetiology. The immune response against normal commensal microorganisms is believed to drive inflammatory processes associated with UC. Therefore, modulation of bacterial communities on the gut mucosa, through the use of probiotics and prebiotics, may be used to modify the disease state. Methods: A synbiotic was developed for use in UC patients combining a probiotic, Bifidobacterium longum , isolated from healthy rectal epithelium, and a prebiotic (Synergy 1), a preferential inulin-oligofructose growth substrate for the probiotic strain. Treatment was employed in a double blinded randomised controlled trial using 18 patients with active UC for a period of one month. Clinical status was scored and rectal biopsies were collected before and after treatment, and transcription levels of epithelium related immune markers were measured. Results: Sigmoidoscopy scores (scale 0–6) were reduced in the test group (start 4.5 (1.4), end 3.1 (2.5)) compared with placebo (start 2.6 (2.1), end 3.2 (2.2)) (p = 0.06). mRNA levels for human beta defensins 2, 3, and 4, which are strongly upregulated in active UC, were significantly reduced in the test group after treatment (p = 0.016, 0.038, and 0.008, respectively). Tumour necrosis factor α and interleukin 1α, which are inflammatory cytokines that drive inflammation and induce defensin expression, were also significantly reduced after treatment (p = 0.018 and 0.023, respectively). Biopsies in the test group had reduced inflammation and regeneration of epithelial tissue. Conclusions: Short term synbiotic treatment of active UC resulted in improvement of the full clinical appearance of chronic inflammation in patients receiving this therapy.

The metabolically healthy but obese individual presents a favorable inflammation profile.

Abstract: 4.8 vs. 45.5 4.4%; not significant), MHO individuals had significantly lower levels of visceral fat, fasting insulin, plasma triglycerides, high-sensitivity C-reactive protein (CRP), and -1 antitrypsin levels and higher levels of high-density lipoprotein cholesterol than at risk individuals (P 0.05). Stepwise regression analysis showed that CRP, fasting triglycerides, and the lean body mass index explained 19.5, 8.5, and 4.0%, respectively, of the variance observed in glucose disposal (total r 2 0.320; P 0.001) Conclusion: Results of the present study indicate that postmenopausal women displaying the MHO phenotype also have a favorable inflammation profile as shown by lower CRP and -1 antitrypsin levels compared with insulin-resistant women. This suggests that a lower inflammation state, as attested by low CRP levels, could play a role in the protective profile of the MHO individual, and this may be associated metabolically to a lower risk for cardiovascular disease. (J Clin Endocrinol Metab 90: 4145–4150, 2005)

Correlation of C‐reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease

Abstract: Introduction: We sought to examine the relationship between C-reactive protein (CRP) and clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease (IBD). Methods: All IBD patients at our institution between January 2002 and August 2003 who had a CRP, colonoscopy, and either small bowel follow-through (SBFT) or CT enterography (CTE) performed within 14 days were identified. Clinical activity was assessed retrospectively through review of the medical record. Logistic regression was used in Crohn's disease (CD) patients to estimate the odds ratio (OR) with 95% confidence intervals for an elevated CRP. Associations were assessed using Fisher exact test in ulcerative colitis (UC) patients due to small sample size. Results: One-hundred four CD patients (46% males) and 43 UC and indeterminate colitis patients (44% males) were identified. In CD patients, moderate-severe clinical activity (OR, 4.5; 95% CI, 1.1-18.3), active disease at colonoscopy (OR, 3.5; 95% CI, 1.4-8.9), and histologically severe inflammation (OR, 10.6; 95% CI; 1.1-104) were all significantly associated with CRP elevation. Abnormal small bowel radiographic imaging was not significantly associated with CRP elevation. In UC patients, CRP elevation was significantly associated with severe clinical activity, elevation in sedimentation rate, anemia, hypoalbuminemia, and active disease at ileocolonoscopy, but not with histologic inflammation. Conclusions: CRP elevation in IBD patients is associated with clinical disease activity, endoscopic inflammation, severely active histologic inflammation (in CD patients), and several other biomarkers of inflammation, but not with radiographic activity.

Systemic Markers of Inflammation in Periodontitis

Abstract: This literature review summarizes current knowledge on the systemic levels of selected markers of inflammation in periodontitis. From samples of peripheral blood the following cellular factors are discussed: total number of white blood cells, red blood cells, and thrombocytes. Further, plasma levels of acute-phase proteins, cytokines, and coagulation factors are reviewed. From the available literature it appears that the total numbers of leukocytes and plasma levels of C-reactive protein are consistently higher in periodontitis patients compared to healthy controls. Numbers of red blood cells and levels of hemoglobin are lower in periodontitis and there is a trend towards anemia of chronic disease. Most systemic markers of inflammation discussed in this review are also regarded as predictive markers for cardiovascular diseases. Therefore, changes in these markers in periodontitis may be part of the explanation why periodontitis is associated with cardiovascular diseases and/or cerebrovascular events in epidemiological studies. It is hypothesized that possibly daily episodes of a bacteremia originating from periodontal lesions are the cause for the changes in systemic markers in periodontitis; the cumulative size of all periodontal lesions in the untreated severe patient may amount to 15 to 20 cm2 .

Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-α) and essential hypertension

Abstract: High blood pressure (HBP) has been associated with elevated C-reactive protein (CRP), a marker of chronic mild inflammation. However, the association between HBP and other inflammatory markers, particularly interleukin 6 (IL-6) and tumour necrosis alpha (TNF-alpha), has not been evaluated in well-controlled studies. We examined the cross-sectional relationship between IL-6, TNF-alpha, and CRP and HBP in a random sample of 196 healthy subjects. All markers were measured in duplicate with high-sensitivity ELISA tests. Three blood pressure (BP) measurments were averaged for the analysis, and subjects with systolic BP >or=140 and/or diastolic BP >or=90 mmHg were considered hypertensive. Log binomial regression was used to estimate multivariate-adjusted prevalence ratios (PR) of HBP. Of the subjects, 40% (79) were hypertensive (mean age: 44 years; range 30-64). After adjustment for age, sex, body mass index, family history of HBP, and the level of the other inflammatory markers, subjects in the second (PR: 3.10, P=0.003), third (PR: 2.32; P=0.031), and fourth quartiles (PR: 2.30; P=0.036) of IL-6 were more than twice as likely to be hypertensive than those in the first quartile. Corresponding PR estimates for TNF-alpha levels were 1.41 (P=0.014) for the second; 1.59 (P=0.001) for the third; and 1.61 (P=0.025) for the fourth quartile. The CRP-HBP association was not statistically significant. Our results suggest that TNF-alpha and IL-6 could be independent risk factors for HBP in apparently healthy subjects. Nevertheless, the temporal relationship between elevated inflammation markers and HBP should be ascertained in prospective cohort studies.

N-Terminal Pro-Brain Natriuretic Peptide, C-Reactive Protein, and Urinary Albumin Levels as Predictors of Mortality and Cardiovascular Events in Older Adults

Abstract: ContextB-type natriuretic peptides have been shown to predict cardiovascular disease in apparently healthy individuals but their predictive ability for mortality and future cardiovascular events compared with C-reactive protein (CRP) and urinary albumin/creatinine ratio is unknown.ObjectiveTo assess the prognostic value of the N-amino terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) vs CRP and urinary albumin/creatinine ratio in an older adult population.Design, Setting, and ParticipantsA population-based prospective study of 764 participants aged 50 to 89 years from a community in Copenhagen, Denmark, in which 658 participants provided blood and urinary samples and were examined between September 1, 1998, and January 24, 2000. Of these participants, 626 without heart or renal failure were enrolled. A subgroup of 537 had no history of cardiovascular disease at baseline. During 5 years of follow-up (to December 31, 2003), 94 participants died and 65 developed a first major cardiovascular event.Main Outcome MeasuresRisk of mortality and first major cardiovascular event by baseline levels of NT-proBNP, CRP, and urinary albumin/creatinine ratio levels.ResultsAfter adjustment for the cardiovascular risk factors of age, sex, smoking, diabetes mellitus, hypertension or ischemic heart disease, total cholesterol, and serum creatinine, the hazard ratio (HR) of mortality for values above the 80th percentile of NT-proBNP was 1.96 (95% confidence interval [CI], 1.21-3.19); for CRP, 1.46 (95% CI, 0.89-2.24); and for urinary albumin/creatinine ratio, 1.88 (95% CI, 1.18-2.98). Additional adjustment for left ventricular systolic dysfunction did not markedly attenuate the predictive value of NT-proBNP (HR, 1.82; 95% CI, 1.11-2.98). The absolute unadjusted increase in mortality risk for participants with values above the 80th percentile vs equal to or below the 80th percentile was 24.5% for NT-proBNP, 7.8% for CRP, and 19.5% for urinary albumin/creatinine ratio. The NT-proBNP levels were associated with first major cardiovascular events (nonfatal myocardial infarction, fatal coronary heart disease, unstable angina, heart failure, stroke, and transient ischemic attack) with an adjusted HR of 3.24 (95% CI, 1.80-5.79) vs 1.02 (95% CI, 0.56-1.85) for CRP and 2.32 (95% CI, 1.33-4.05) for urinary albumin/creatinine ratio when comparing participants with values above the 80th percentile with those with values equal to or below the 80th percentile.ConclusionsMeasurements of NT-proBNP provide prognostic information of mortality and first major cardiovascular events beyond traditional risk factors. NT-proBNP was a stronger risk biomarker for cardiovascular disease and death than CRP was in nonhospitalized individuals aged 50 to 89 years.

C-Reactive Protein, Interleukin-6, and Soluble Adhesion Molecules as Predictors of Progressive Peripheral Atherosclerosis in the General Population Edinburgh Artery Study

Abstract: Background— The relationship between levels of circulating inflammatory markers and risk of progressive atherosclerosis is relatively undetermined. We therefore studied inflammatory markers as predictors of peripheral atherosclerotic progression, measured by the ankle-brachial index (ABI) at 3 consecutive time points over 12 years. Methods and Results— The Edinburgh Artery Study is a population cohort study of 1592 men and women aged 55 to 74 years. C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin were measured at baseline. Valid ABI measurements were obtained on 1582, 1081, and 813 participants at baseline and 5-year and 12-year follow-up examinations, respectively. At baseline, a significant trend was found between higher plasma levels of CRP (P≤0.05) and increasing severity of peripheral arterial disease (PAD), after adjustment for baseline cardiovascular risk factors. IL-6 at baseline (P≤0.001) was associa...

A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients

Abstract: Objectives: The cytokine interleukin (IL)-1 mediates ischaemic brain damage in rodents. The endogenous, highly selective, IL-1 receptor antagonist (IL-1ra) protects against ischaemic cerebral injury in a range of experimental settings, and IL-1ra causes a marked reduction of cell death when administered peripherally or at a delay in transient cerebral ischaemia. We report here the first randomised, double blind, placebo controlled trial of recombinant human IL-1ra (rhIL-1ra) in patients with acute stroke. Methods: Patients within 6 hours of the onset of symptoms of acute stroke were randomised to rhIL-1ra or matching placebo. Test treatment was administered intravenously by a 100 mg loading dose over 60 seconds, followed by a 2 mg/kg/h infusion over 72 h. Adverse events and serious adverse events were recorded for up to 3 months, serial blood samples were collected for biological markers up to 3 months, and 5–7 day brain infarct volume was measured by computed tomography. Results: No adverse events were attributed to study treatment among 34 patients randomised. Markers of biological activity, including neutrophil and total white cell counts, C reactive protein, and IL-6 concentrations, were lower in rhIL-1ra treated patients. Among patients with cortical infarcts, clinical outcomes at 3 months in the rhIL-1ra treated group were better than in placebo treated. Conclusions: These data suggest that rhIL-1ra is safe and well tolerated in acute stroke. In addition, rhIL-1ra exhibited biological activity that is relevant to the pathophysiology and clinical outcome of ischaemic stroke. Our findings identify rhIL-1ra as a potential new therapeutic agent for acute stroke.

Short-term Effects of Intensive Periodontal Therapy on Serum Inflammatory Markers and Cholesterol

Abstract: Severe periodontitis has been associated with increased systemic inflammation. In a three-arm preliminary randomized trial, we investigated the impact of standard (SPT) and intensive periodontal therapy (IPT) on serum inflammatory markers and cholesterol levels. Medical and periodontal parameters, C-reactive protein (CRP), interleukin-6 (IL-6), total cholesterol, and LDL cholesterol were evaluated in 65 systemically healthy subjects suffering from severe generalized periodontitis. Two months after treatment, both SPT and IPT resulted in significant reductions in serum CRP compared with the untreated control (0.5 +/- 0.2 mg/L for SPT, P = 0.030 and 0.8 +/- 0.2 mg/L for IPT, P = 0.001). Similar results were observed for IL-6. Changes in inflammation were independent of age, gender, body mass index, and ethnicity, but a significant interaction between cigarette smoking and treatment regimen was found. The IPT group also showed a decrease in total and LDL cholesterol after 2 months. Analysis of these data indicates that periodontitis causes moderate systemic inflammation in systemically healthy subjects.

Progression of age-related macular degeneration: prospective assessment of C-reactive protein, interleukin 6, and other cardiovascular biomarkers.

Abstract: Background Age-related macular degeneration (AMD) and cardiovascular disease share common risk factors. Inflammatory biomarkers, including C-reactive protein (CRP), interleukin 6 (IL-6), soluble tumor necrosis factor alpha receptor 2, soluble intercellular and vascular adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1), and lipid biomarkers, including lipoprotein(a) and apolipoprotein B, have all been associated with cardiovascular disease. We previously found an association between AMD and CRP in a cross-sectional analysis, but the prospective relationships between AMD, CRP, and the other cardiovascular disease markers are unknown. Objective To test the hypothesis that baseline cardiovascular disease biomarkers are associated with subsequent increased risk for progression of AMD. Design, Setting, and Participants This prospective cohort study involved 251 participants aged 60 years and older who had some sign of nonexudative AMD and visual acuity of 20/200 or better in at least one eye at baseline. The AMD status was assessed by standardized grading of fundus photographs, and stored fasting blood specimens obtained at baseline were analyzed for levels of the various biomarkers. The average follow-up time was 4.6 years. Main Outcome Measures Relationship between biomarkers and incidence rates of progression of AMD. Results Comparing the highest quartile with the lowest quartile, CRP was associated with progression of AMD, with a multivariate adjusted relative risk (RR) of 2.10 (95% confidence interval [CI], 1.06-4.18; P for trend, .046) controlling for body mass index, smoking, and other cardiovascular variables and a multivariate adjusted RR of 2.02 (95% CI, 1.00-4.04; P for trend, .06) controlling additionally for antioxidant nutrients. Interleukin 6 was also related to progression of AMD, with a multivariate adjusted RR of 1.81 (95% CI, 0.97-3.36; P for trend, .03). Comparing the highest quartile with the lowest quartile, the effect estimates for vascular cell adhesion molecule 1 (multivariate adjusted RR, 1.94) and apolipoprotein B (adjusted RR, 1.39) were in the positive direction but were not statistically significant ( P for trend, .08 and .24, respectively). The CRP and IL-6 levels were both significantly related to higher body mass index and current smoking. Conclusions Higher levels of the systemic inflammatory markers CRP and IL-6 are independently associated with progression of AMD.

Arterial Stiffness Is Related to Systemic Inflammation in Essential Hypertension

Abstract: The acute phase–reactant high-sensitivity C-reactive protein, a marker of vascular inflammation and an atherosclerotic risk factor, is related to arterial stiffness in healthy subjects and in systemic vasculitis. To explore the relationship between markers of inflammation, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein with arterial stiffness, we studied untreated patients (n=78; 56% male; 47±1 years of age; mean±SEM) with essential hypertension. After overnight fast, augmentation index and pulse wave velocity were assessed noninvasively and related to plasma levels of inflammatory markers measured by ELISA. Pulse wave velocity was significantly related to plasma high-sensitivity C-reactive protein ( r =0.31; P r =0.30; P r =0.21; P r =0.37; P r =0.24; P r =0.19, P =0.06). High-sensitivity C-reactive protein was an independent predictor of pulse wave velocity and augmentation index in a multiple stepwise regression model. High-sensitivity C-reactive protein, a marker of systemic inflammation, is independently related to pulse wave velocity, a marker of aortic stiffness, and augmentation index, a manifestation of wave reflection, in essential hypertension.

C-reactive protein, antiproteases and complement factors as objective markers of severity in acute pancreatitis.

Abstract: In a series of patients with acute pancreatitis we have studied complement factors, antiproteases (alpha 2-macroglobulin and alpha 1-antiprotease) and C-reactive protein to determine the value of their sequential measurement in the prediction of outcome relative to clinical assessment and current multiple factor scoring systems. Complement factors were unhelpful in predicting the severity of an attack. alpha 2-Macroglobulin levels were significantly lower in complicated attacks during days 3-8 and alpha 1-antiprotease levels were significantly higher during days 4-8. C-reactive protein concentrations showed the best discrimination between mild and complicated attacks, levels rising higher and persisting for longer in complicated attacks; these differences were highly significant from day 2 (the morning after admission) to day 8. The concentrations providing the best discrimination were found to be greater than or equal to 210 mg/l for the peak C-reactive protein (on the second, third or fourth day) and greater than or equal to 120 mg/l for the C-reactive protein at the end of the first week. Analysis demonstrated both the peak or seventh-day C-reactive protein concentration to be of similar accuracy to either the Ranson or Glasgow multiple factor scoring systems and slightly better for attacks associated with gallstones. The C-reactive protein assay is simple, quick to perform, provides useful clinical information and is more likely to be of value and to be adopted into routine clinical practice than multiple factor scoring systems.

Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients

Abstract: Background. Fetuin-A (a2-Heremans Schmid glycoprotein) has recently been identified as a circulating inhibitor of calcification and is regulated as a negative acute phase protein. However, its relationships with cardiac valvular calcification and atherosclerosis and outcome have not been evaluated in peritoneal dialysis (PD) patients. Method. We performed a prospective follow-up study in 238 PD patients with echocardiography done at baseline to detect cardiac valvular calcification and biochemical analysis performed for serum fetuin-A, albumin and C-reactive protein (CRP). Results. Baseline serum fetuin-A concentration was (mean±SD) 0.309±0.068 g/l (normal range 0.4–0.95). Across the three tertiles of increasing serum fetuin-A, a significant trend effect was observed for age (P ¼ 0.023), diabetes (P ¼ 0.008), background atherosclerotic vascular disease (P ¼ 0.010), cardiac valvular calcification (P ¼ 0.002), serum albumin (P<0.001), subjective global assessment (P ¼ 0.005) and CRP (P<0.001). Adjusting for CRP and calcium � phosphorus product, every 0.01 g/l increase in serum fetuin-A remained independently associated with a 6% decrease in the risk of valvular calcification (95% confidence intervals, 0.90–0.99; P ¼ 0.028). Furthermore, serum fetuin-A showed a significant decrease across the four groups of patients with increasing components of the malnutrition, inflammation, atherosclerosis/calcification (MIAC) syndrome (P<0.001) and was the lowest among patients with all components of the MIAC syndrome (0.263±0.055 g/l) and highest among those who do not have the MIAC syndrome at all (0.338±0.063 g/l). Lower serum fetuin-A was associated with greater all-cause mortality (P ¼ 0.0011) and fatal and non-fatal cardiovascular events (P ¼ 0.0017), but its significance was lost when atherosclerotic vascular disease, valvular calcification, inflammation and malnutrition were included in the model. Conclusions. Serum fetuin-A showed important associations with valvular calcification, atherosclerosis, malnutrition and inflammation, and was linked to mortality and cardiovascular events in PD patients via its close relationships with the MIAC syndrome.

Acute-Phase Markers of Inflammation and Glomerular Structure in Patients with Type 2 Diabetes

Abstract: Type 2 diabetes is frequently associated with an inflammatory status; the relationships between low-grade inflammation and diabetic nephropathy are still unclear. The aim of this study was to evaluate the relationships between acute-phase markers of inflammation, glomerular structure, and albumin excretion rate (AER) in type 2 diabetes. In 74 patients with type 2 diabetes (23 normoalbuminuric, 30 microalbuminuric, and 21 proteinuric) fibrinogen, serum amyloid A protein (SAA), C-reactive protein (CRP), and IL-6 were determined. AER was measured on three 24-h urine collections; GFR was measured by 51Cr EDTA plasma clearance. A kidney biopsy was performed, and mesangial fractional volume [Vv(mes/glom)] and glomerular basement membrane (GBM) width were estimated by electron microscopic morphometric analysis. CRP, fibrinogen, SAA, and IL-6 differed among groups, with proteinuric patients having the highest levels. SAA and fibrinogen correlated with AER (P 396 nm), CRP, SAA, and IL-6 were higher than in patients with normal GBM width (P < 0.003, P < 0.004, and P < 0.0004, respectively). GBM width was directly correlated with fibrinogen (r = 0.33, P < 0.002) and IL-6 (r = 0.25 P < 0.05). In conclusion, this study demonstrates that acute-phase markers of inflammation are associated with nephropathy status and GBM thickening, suggesting a role for inflammation in the pathogenesis of diabetic glomerulopathy.

Markers of inflammation are cross-sectionally associated with microvascular complications and cardiovascular disease in type 1 diabetes--the EURODIAB Prospective Complications Study

Abstract: The pathogenesis of vascular complications in type 1 diabetes is poorly understood, but may involve chronic, low-grade inflammation. We investigated the association of markers of inflammation with vascular complications in type 1 diabetes. A cross-sectional nested case-control study of the follow-up data of the EURODIAB Prospective Complications Study. This study included 543 individuals (278 men) with type 1 diabetes diagnosed at <36 years of age. Cases (n=348) had complications of diabetes, controls (n=195) had no complications. C-reactive protein, interleukin-6 and tumour necrosis factor-α levels, which were combined in an inflammatory marker Z-score, were associated with albuminuria, retinopathy and cardiovascular disease. Calculated means (95% confidence intervals) of the marker Z-score were −0.15 (−0.22 to −0.07), 0.10 (−0.05 to 0.25), and 0.28 (0.15 to 0.41), p for trend <0.0001, in individuals with normo-, micro- and macroalbuminuria; −0.23 (−0.33 to −0.13), 0.14 (0.02 to 0.25) and 0.20 (0.07 to 0.32), p for trend <0.0001, in individuals with no, non-proliferative and proliferative retinopathy; and −0.28 (−0.39 to −0.18) and 0.06 (−0.08 to 0.20), p<0.001, in individuals without and with cardiovascular disease. Per 1 SD increase of the inflammatory marker Z-score, GFR decreased by −4.6 (−6.6 to −2.6) ml per min per 1.73 m2 (p<0.001). We have shown that markers of inflammation are strongly and independently associated with microvascular complications and cardiovascular disease in type 1 diabetes. These data suggest that strategies to decrease inflammatory activity may help to prevent the development of vascular complications in type 1 diabetes.

Statins Reduce Interleukin-6–Induced C-Reactive Protein in Human Hepatocytes: New Evidence for Direct Antiinflammatory Effects of Statins

Abstract: Objectives— Besides its predictive role in determining cardiovascular risk, C-reactive protein (CRP) may exert direct proatherogenic effects through proinflammatory properties. CRP is mainly produced by hepatocytes in response to interleukin-6 (IL-6) and is then released into the systemic circulation. 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors, or statins, significantly reduce cardiovascular events and mortality in patients with or without coronary artery disease and reduce plasma CRP levels in humans. However, the mechanism by which statins reduce plasma CRP levels remains unknown. Methods and Results— In this study, we report that statins limit both protein and RNA levels of IL-6-induced CRP in human hepatocytes. These effects are reversed by l-mevalonate and mimicked by an inhibitor of the geranylgeranyltransferase. IL-6–induced CRP production requires the binding of IL-6 to its cognate receptors, which results in activation and phosphorylation of the transcription factor ST...

Serum concentrations of inflammatory mediators related to organ failure in patients with acute pancreatitis

Abstract: Leucocyte activation and proinflammatory cytokine release (tumour necrosis factor (TNF) and interleukin 6 (IL-6)) are thought to contribute to the induction of a systemic inflammatory response, an acute-phase response and multiple organ failure in patients with acute pancreatitis. The serum concentration of TNF, soluble TNF receptors (sTNFR55 and sTNFR75), IL-6 and C-reative protein (CRP) in 58 patients with acute pancreatitis was assessed during the first 2 days of admission. Thirty patients had mild disease and 28 severe disease, of whom 18 developed local pancreatic complications alone (Atlanta classification) and ten developed organ failure (a Goris score of 1 or more). TNF was detected in only 17 patients on the first day of admission, while soluble TNF receptors were detected in all patients and IL-6 in 34. On the first and second days of admission there was a progressive and significant (P < 0.03) increase in the median concentration of sTNFR55, sTNFR75 and IL-6 in patients eventually classified into those with mild disease, a local pancreatic complication alone, or organ failure. This pattern was also evident in CRP levels from the second but not the first day of admission. These findings suggest that proinflammatory cytokines or their soluble receptors may be more accurate early predictors of outcome than CRP, Moreover, markers of inflammation in the sera of patients with acute pancreatitis are highest in those who subsequently develop organ failure.

Behavioural treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training.

Abstract: PERSISTENT LOW-GRADE INFLAMMATION, as indicated by higher circulating levels of inflammatory mediators such as C-reactive protein, interleukin-6 and tumour necrosis factor-α, is a strong risk factor for several chronic diseases. There are data indicating that decreasing energy intake and increasing physical activity may be effective therapies for reducing overall inflammation. Evidence is strong that circulating levels of inflammatory markers are elevated with total and abdominal obesity, possibly owing to a higher secretion rate of cytokines by adipose tissue in obese people. Moreover, very-low-energy dietary weight loss reduces both circulating markers of inflammation and adipose-tissue cytokine production. Data from several large population-based cohorts show an inverse association between markers of systemic inflammation and physical activity or fitness status; small-scale intervention studies support that exercise training diminishes inflammation. Dietary weight loss plus exercise is likely more effective than weight reduction alone in reducing inflammation. To date, data from randomized, controlled trails designed to definitively test the effects of weight loss or exercise training, or both, on inflammation are limited. Future studies are required to define the amount of weight loss needed for clinically meaningful reductions of inflammation; in addition, fully powered and controlled studies are necessary to clarify the effect of exercise training on chronic, systemic inflammation.

Influence of anti-tumour necrosis factor therapy on cardiovascular risk factors in patients with active rheumatoid arthritis.

Abstract: BACKGROUND: Tumour necrosis factor (TNF) is known to increase the concentrations of interleukin (IL) 6 and C reactive protein (CRP) and to induce proatherogenic changes in the lipid profile and may increase the cardiovascular risk of patients with rheumatoid arthritis (RA) and other inflammatory disorders. OBJECTIVE: To assess whether anti-TNF therapy modifies the cardiovascular risk profile in patients with RA. METHODS: The lipoprotein spectrum and the inflammation markers CRP and IL6 were investigated in 33 patients with RA treated with human anti-TNF monoclonal antibodies (D2E7, adalimumab, Humira) and 13 patients with RA given placebo, before and after 2 weeks' treatment. RESULTS: In the anti-TNF treated group, the mean (SD) concentrations of HDL-cholesterol were significantly higher after 2 weeks' treatment (0.86 (0.30) mmol/l v 0.98 (0.33) mmol/l, p<0.01), whereas LDL and triglyceride levels were not significantly changed. Additionally, a significant decrease in CRP (86.1 (54.4) mg/l v 35.4 (35.0) mg/l, p<0.0001), and IL6 (88.3 (60.5) pg/ml v 42.3 (40.7) pg/ml, p<0.001) concentrations was seen in this group. No changes in lipid profile, IL6, or CRP levels were seen in the placebo group. CONCLUSIONS: TNF neutralisation with monoclonal anti-TNF antibodies increased HDL-cholesterol levels and decreased CRP and IL6 levels after 2 weeks. Therefore this treatment may improve the cardiovascular risk profile of patients with RA.

Association of lipoprotein-associated phospholipase A2 levels with coronary artery disease risk factors, angiographic coronary artery disease, and major adverse events at follow-up

Abstract: Aims We aimed to evaluate the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) with coronary artery disease (CAD) risk factors, with the severity of angiographic CAD, and with the incidence of major adverse events Methods and results We measured Lp-PLA2 levels in 504 consecutive patients undergoing clinically indicated coronary angiography Mean age was 60±11 years and 38% were women The mean (±SD) Lp-PLA2 level (ng/mL) was 245±91 Lp-PLA2 levels correlated with male gender, LDL, HDL, and total cholesterol, fibrinogen, and creatinine Lp-PLA2 levels correlated with the extent of angiographic CAD on univariate but not on multivariable analysis During a median follow-up of 40 years, 72 major adverse events occurred in 61 of 466 (13%) contacted patients (20 deaths, 14 myocardial infarctions, 28 coronary revascularizations, and 10 strokes) Higher Lp-PLA2 levels were associated with a greater risk of events: the hazard ratio per SD was 128 (95% CI 106–154, P =0009), and remained significant after adjusting for clinical and lipid variables and C-reactive protein Conclusion Higher Lp-PLA2 levels were associated with a higher incidence of major adverse events at follow-up, independently of traditional CAD risk factors and C-reactive protein

Effect of exercise training on plasma levels of C-reactive protein in healthy adults: the HERITAGE Family Study

Abstract: Aims To study the effect of exercise training on plasma C-reactive protein, a marker of inflammation. Methods and results We performed a 20 week standardized exercise training programme in 652 sedentary healthy white and black men and women. C-reactive protein was measured with a high sensitivity assay. The study sample was stratified according to baseline C-reactive protein levels using a recommended classification (low 3.0 mg/L, n =162). The median C-reactive protein reduction was 1.34 mg/L in the high baseline C-reactive protein group. C-reactive protein levels did not change in the low or moderate baseline C-reactive protein groups. The difference among the C-reactive protein groups was significant adjusting for all correlates of baseline C-reactive protein ( P <0.001) and additionally for changes in body weight, glucose, insulin, LDL cholesterol, HDL cholesterol, triglycerides, systolic and diastolic blood pressure, and maximal oxygen uptake ( P <0.001). The C-reactive protein reduction in the high baseline C-reactive protein group was consistent across all population groups ( P <0.001 for difference among baseline C-reactive protein groups). Conclusion Plasma C-reactive protein levels are reduced in response to exercise training in sedentary healthy adults with high initial C-reactive protein levels. This finding may partly explain the effectiveness of regular physical activity in the prevention and treatment of cardiovascular and metabolic diseases.

Central Fat Excess in Polycystic Ovary Syndrome: Relation to Low-Grade Inflammation and Insulin Resistance

Abstract: Results: Compared with controls, patients with PCOS had a higher trunk to extremity fat ratio (T/E fat), were more insulin resistant (higherhomeostasismodelassessmentofinsulinresistanceandlower SHBG concentrations), and had higher levels of highly sensitive Creactive protein, TNF-, procalcitonin, and white blood cell count (all P 0.04), even after adjusting for total body fat. However, additional adjusting for T/E fat eliminated or attenuated the effect of PCOS status on estimates of insulin resistance, on inflammatory mediators, and on white blood cell count but not on circulating sex hormones. Independently of each other, total body fat as well as T/E fat correlated with estimates of insulin resistance and most inflammatory mediators (P 0.04). However, the correlations between T/E fat and circulating sex hormones (P 0.02) were greatly reduced after adjustment for the presence of PCOS. Conclusion: The increase in low-grade chronic inflammation and in insulin resistance in women with PCOS is primarily associated with increased central fat excess rather than PCOS status per se. Procalcitoninrepresentsanovelmarkeroftheinflammatoryactivityofbody fat and of PCOS. (J Clin Endocrinol Metab 90: 6014–6021, 2005)

Total antioxidant capacity of the diet is inversely and independently related to plasma concentration of high-sensitivity C-reactive protein in adult Italian subjects

Abstract: Inflammation, a risk factor for cardiovascular disease, is associated with low plasma levels of antioxidant vitamins. In addition to vitamins, other antioxidants modulate the synthesis of inflammatory markers in vitro and contribute to the total antioxidant capacity (TAC) of a diet. However, the relationship between dietary TAC and markers of inflammation has never been evaluated in vivo. We investigated the relationship between dietary TAC and markers of systemic (high-sensitivity C-reactive protein (hs-CRP), leucocytes) and vascular (soluble intercellular cell adhesion molecule-1) inflammation in 243 non-diabetic subjects. General Linear Model (GLM) analysis showed a significant (P=0.005) inverse relationship between hs-CRP and quartiles of energy-adjusted dietary TAC, even when recognized modulating factors of inflammation, namely alcohol, fibre, vitamin C, alpha-tocopherol, beta-carotene, BMI, waist circumference, HDL-cholesterol, hypertension, insulin sensitivity and plasma beta-carotene, were included in the model as covariates (P=0.004). The relationship was stronger for subjects with hypertension (P=0.013 v. P=0.109 for normotensive individuals). Among dietary factors, TAC was significantly higher (5.3 (sd 3.0) v. 4.9 (sd 2.7) mmol Trolox/d; P=0.026) in subjects with low plasma hs-CRP (range: 0.0-4.1 mg/l) than in subjects with high plasma hs-CRP (range: 4.2-27.8 mg/l). We conclude that dietary TAC is inversely and independently correlated with plasma concentrations of hs-CRP and this could be one of the mechanisms explaining the protective effects against CVD of antioxidant-rich foods such as fruits, whole cereals and red wine. This could be of particular significance for subjects with high blood pressure.

Activation of Inflammation and Coagulation After Infusion of C-Reactive Protein in Humans

Abstract: C-reactive protein (CRP) has been postulated to play a causal part in atherosclerosis and its acute complications. We assessed the effects of CRP-infusion on coagulation and inflammatory pathways to determine its role in atherothrombotic disease. Seven male volunteers received an infusion on two occasions, containing 1.25 mg/kg recombinant human CRP (rhCRP) or diluent, respectively. CRP-concentrations rose after rhCRP-infusion from 1.9 (0.3 to 8.5) to 23.9 (20.5 to 28.1) mg/L, and subsequently both inflammation and coagulation were activated. This sequence of events suggests that CRP is not only a well known marker of cardiovascular disease, but is also probably a mediator of atherothrombotic disease.