Camila Renata Corrêa

Smoking status and tumor necrosis factor-alpha mediated systemic inflammation in COPD patients

BackgroundSmoking cause airway and systemic inflammation and COPD patients present low grade inflammation in peripheral blood. However, data on the influence of smoking itself on systemic inflammation in COPD patients are scarce. This study investigated the association between inflammation, smoking status, and disease.MethodsA cross-sectional analysis comparing 53 COPD ex-smokers, 24 COPD current smokers, 24 current smoker controls and 34 never-smoker controls was performed. Assessments included medical history, body composition, spirometry, and plasma concentration of tumor necrosis factor-alpha (TNF-α), interleukins (IL)-6, IL-8, and C-reactive protein (CRP).ResultsOur exploratory analysis showed that serum TNF-α was higher in COPD current smokers [4.8(4.2-5.8)pg/mL] and in current smoker controls [4.8 (4.2-6.1) pg/mL] when compared to COPD ex-smokers [4.3 (3.9-4.9)pg/mL; p = 0.02] and to never-smoker controls [3.7 (3.4-4.0)pg/mL; p < 0.001]. Multiple regression results with and without adjustment for covariates were consistent with the hypothesis that TNF-α levels were associated with smoking status in both models (p < 0.001 and p < 0.001). IL-6 and CRP were significantly higher in COPD patients when compared to smoker and never-smoker controls and the multiple regression analysis confirmed the association of these mediators with disease, but not with smoking status (p < 0.001 and p < 0.001). IL-8 had only a borderline association with disease in both models (p = 0.069 and p = 0.053). No influence of disease severity, inhaled corticosteroid, fat-free mass (FFM) depletion and long term oxygen therapy (LTOT) use on systemic inflammation was found.ConclusionSmoking may influence TNF-α mediated systemic inflammation, which, in turn, may account for some of the benefits observed in patients with COPD who stop smoking.

Comparison of ω-3 fatty acids and sulfasalazine in ulcerative colitis

Fish oil omega-3 fatty acids exert antiinflammatory effects on patients with ulcerative colitis. However, a comparative study in patients with mild to moderate ulcerative colitis receiving only sulfasalazine or omega-3 fatty acids has not been performed. We sought to detect changes in the inflammatory disease activity with the use of either fish oil omega-3 fatty acids or sulfasalazine in patients with ulcerative colitis. Ten patients (five male, five female; mean age = 48 +/- 12 y) with mild to moderate active ulcerative colitis were investigated in a randomized cross-over design. They received either sulfasalazine (2 g/d) or omega-3 fatty acids (5.4 g/d) for 2 m.o. Disease activity was assessed by clinical and laboratory indicators, sigmoidoscopy, histology, and whole-body protein turnover (with 15N-glycine). Treatment with omega-3 fatty acids resulted in greater disease activity as detected by a significant increase in platelet count, erythrocyte sedimentation rate, C-reactive protein, and total fecal nitrogen excretion. No major changes in protein synthesis and breakdown were observed during either treatment. In conclusion, treatment with sulfasalazine is superior to treatment with omega-3 fatty acids in patients with mild to moderate active ulcerative colitis.

Three-year follow-up of Interleukin 6 and C-reactive protein in chronic obstructive pulmonary disease

BackgroundPast studies have shown that mean values of Interleukin-6 (IL-6) and C-reactive protein (CRP) do not change significantly in COPD patients over a one-year period. However, longer period follow-up studies are still lacking. Thus, the aim of this study is to evaluate plasma CRP and IL-6 concentration over three years in COPD patients and to test the association between these inflammatory mediators and disease outcome markers.MethodsA cohort of 77 outpatients with stable COPD was evaluated at baseline, and 53 (mean FEV1, 56% predicted) were included in the prospective study. We evaluated Interleukin-6 (IL-6), C-reactive protein (CRP), six-minute walking distance (6MWD), and body mass index (BMI) at baseline and after three years. Plasma concentration of IL-6 was measured by high sensitivity ELISA, and CRP was obtained by high sensitivity particle-enhanced immunonephelometry.ResultsIL-6 increased significantly after 3 years compared to baseline measurements [0.8 (0.5-1.3) vs 2.4 (1.3-4.4) pg/ml; pu2009<u20090.001] and was associated with worse 6MWD performance. In the Cox regression, increased IL-6 at baseline was associated with mortality [Hazard Ratio (95% CI)u2009=u20092.68 (0.13, 1.84); pu2009=u20090.02]. CRP mean values did not change [5 (1.6-7.9) vs 4.7 (1.7-10) pg/L; pu2009=u20090.84], although eleven patients (21%) presented with changes >3 mg/L in CRP after 3 years.ConclusionsThe systemic inflammatory process, evaluated by IL-6, seems to be persistent, progressive and associated with mortality and worse physical performance in COPD patients.Trial registrationNo.:NCT00605540

Lycopene supplementation modulates plasma concentrations and epididymal adipose tissue mRNA of leptin, resistin and IL-6 in diet-induced obese rats

Obesity is characterised by chronic low-grade inflammation, and lycopene has been reported to display anti-inflammatory effects. However, it is not clear whether lycopene supplementation modulates adipokine levels in vivo in obesity. To determine whether lycopene supplementation can regulate adipokine expression in obesity, male Wistar rats were randomly assigned to receive a control diet (C, n 6) ora hyperenergetic diet (DIO, n 12) for 6 weeks. After this period, the DIO animals were randomised into two groups: DIO (n 6) and DIO supplemented with lycopene (DIO + L, n 6). The animals received maize oil (C and DIO) or lycopene (DIO + L, 10 mg/kg body weight(BW) per d) by oral administration for a 6-week period. The animals were then killed by decapitation, and blood samples and epididymal adipose tissue were collected for hormonal determination and gene expression evaluation (IL-6, monocyte chemoattractant protein-1(MCP-1), TNF-α, leptin and resistin). There was no detectable lycopene in the plasma of the C and DIO groups. However, the mean lycopene plasma concentration was 24 nmol in the DIO + L group. Although lycopene supplementation did not affect BW or adiposity, it significantly decreased leptin, resistin and IL-6 gene expression in epididymal adipose tissue and plasma concentrations. Also, it significantly reduced the gene expression of MCP-1 in epididymal adipose tissue. Lycopene affects adipokines by reducing leptin, resistin and plasma IL-6 levels. These data suggest that lycopene may be an effective strategy in reducing inflammation in obesity.

Comparação entre a relação PCR/albumina e o índice prognóstico inflamatório nutricional (IPIN)

The inflammatory stress of hospitalyzed patients was quantified according to their plasma levels of acute-phase proteins (APP). The data from 54 adult (48 ± 20 yrs) patients were retrospectively (1994-1998) analysed along with other 12 healthy controls. The major pathologies were peripheral vascular disease (22) , penphigus pholiaceos (7), inflammatory bowel disease (7), trauma (6) and orthognatic post surgery (3). Samples of fasting venous blood were drawn and their plasma used for positive (+) and negative (-) APP by nephelometric assays. Among assayed APP+ were C-reactive protein (CRP), acid a-1-glycoprotein (AAG), a-1-antitrypsin (AAT) and ceruloplasmim (CER) while albumin (Alb), transthyretin (TTR), transferrin (TF) and retinol-binding protein (RBP) were the APP- representatives. A significant relationship (Spearman test) was found between the variables CRP ´ AAG (r = 0.49), Alb ´ TTR (r = 0.60), Alb ´ RBP (0.58), Alb ´ TF (r = 0.39), TTR ´ RBP (r = 0.56) and TTR ´TF (r = 0.43). The stronger relationships between APP+ ´ APP- were found for CRP ´ Alb (r = - 0.71), CRP ´ TTR (- 0.54), CRP ´ TF (r = - 0.39) and AAG ´ Alb (r = - 0.35). By assembling the APP according to the prognostic inflammatory nutritional index (PINI) proposed by Ingenbleek & Carpentier (Int. J. Vitam. Nutr. Res., 55: 91, 1985) the obtained data allowed a group distribution as healthy controls (G1), patients without (PINI 1, G3). The later was split as lower (G3A, n =16) medium (G3B, n =10) and high (G3C, n = 6) risk and mortality-risk (G3D, n =11). The PINI values differentiated (non-parametric Kruskall-Wallis test) G3 > (G1= G2) and G3 > G3A. Among all assayed proteins only CRP, Alb and TTR discriminated groups as G3 > (G1= G2) for CRP or G3 G3A (for CRP) and G3D < G3A (for TTR and TF). The correlation coeficient allowed only APP¾ substitutions at the PINI formula whereas CRP/Alb was the best PINI simplification form keeping its power of group discrimination.

Effects of Active Smoking on Airway and Systemic Inflammation Profiles in Patients With Chronic Obstructive Pulmonary Disease

Background:The markers that characterize local and systemic inflammation in chronic obstructive pulmonary disease (COPD) remain unclear, as do their correlations with smoking status and presence of disease. The aim of this study was to assess markers of inflammation in the peripheral blood and airways of current smokers without COPD, of current smokers with COPD and of ex-smokers with COPD. Methods:In this study, 17 current smokers with COPD (mean age: 58.2 ± 9.6 years; mean forced expiratory volume in 1 second [FEV1]: 56.1 ± 15.9%), 35 ex-smokers with COPD (mean age: 66.3 ± 7.3 years; mean FEV1: 47.9 ± 17.2%) and 20 current smokers without COPD (mean age: 49.1 ± 6.2 years; mean FEV1: 106.5 ± 15.8%) were evaluated. Spirometry findings, body composition and serum/induced sputum concentrations of tumor necrosis factor &agr; (TNF-&agr;), interleukin (IL)-6, IL-8 and IL-10, together with serum C-reactive protein (CRP) levels, were assessed. Results:Serum TNF-&agr; concentration was higher in all current smokers than in ex-smokers with COPD. In current smokers without COPD, serum CRP level was lower than in ex-smokers with COPD and significantly lower than in current smokers with COPD. Sputum TNF-&agr; concentration was higher in current and ex-smokers with COPD than in current smokers without COPD. Multiple regression analyses showed that serum TNF-&agr; was associated with active smoking, and serum CRP and sputum TNF-&agr; were associated with COPD diagnosis. Conclusions:Smoking is associated with higher systemic inflammation in patients with COPD. Current findings also support the hypothesis that smoking and COPD have different effects on the regulation of airway and systemic inflammatory processes.

Activation of monocytes and cytokine production in patients with peripheral atherosclerosis obliterans.

BackgroundArterial peripheral disease is a condition caused by the blocked blood flow resulting from arterial cholesterol deposits within the arms, legs and aorta. Studies have shown that macrophages in atherosclerotic plaque are highly activated, which makes these cells important antigen-presenting cells that develop a specific immune response, in which LDLox is the inducing antigen. As functional changes of cells which participate in the atherogenesis process may occur in the peripheral blood, the objectives of the present study were to evaluate plasma levels of anti-inflammatory and inflammatory cytokines including TNF-α, IFN-γ, interleukin-6 (IL-6), IL-10 and TGF-β in patients with peripheral arteriosclerosis obliterans, to assess the monocyte activation level in peripheral blood through the ability of these cells to release hydrogen peroxide (H2O2) and to develop fungicidal activity against Candida albicans (C. albicans) in vitro.MethodsTNF-α, IFN-γ, IL-6, IL-10 and TGF-β from plasma of patients were detected by ELISA. Monocyte cultures activated in vitro with TNF-alpha and IFN-gamma were evaluated by fungicidal activity against C. albicans by culture plating and Colony Forming Unit (CFU) recovery, and by H2O2 production.ResultsPlasma levels of all cytokines were significantly higher in patients compared to those detected in control subjects. Control group monocytes did not release substantial levels of H2O2in vitro, but these levels were significantly increased after activation with IFN-γ and TNF-α. Monocytes of patients, before and after activation, responded less than those of control subjects. Similar results were found when fungicidal activity was evaluated. The results seen in patients were always significantly smaller than among control subjects. Conclusions: The results revealed an unresponsiveness of patient monocytes in vitro probably due to the high activation process occurring in vivo as corroborated by high plasma cytokine levels.

DNA damage in peripheral blood mononuclear cells of patients undergoing anti-tuberculosis treatment

Tuberculosis (TB), a chronic infectious disease, is a major cause of morbidity and mortality worldwide. Expression of iNOS and consequent production of NO during the inflammatory process is an important defense mechanism against TB bacteria. We have tested whether pulmonary TB patients undergoing anti-tuberculosis treatment present DNA damage, and whether this damage is related to oxidative stress, by evaluating total hydrophilic antioxidant capacity and iNOS expression. DNA damage in peripheral blood mononuclear cells from patients and healthy tuberculin test (PPD) positive controls was evaluated by single-cell gel electrophoresis (comet assay), and iNOS expression was measured by qPCR. We also evaluated total hydrophilic antioxidant capacity in plasma from patients and controls. Compared to controls, pulmonary TB patients under treatment presented increased DNA damage, which diminished during treatment. Also, the antioxidant capacity of these individuals was increased at the start of treatment, and reduced during treatment. TB patients showed lower iNOS expression, but expression tended to increase during treatment. Our results indicate that pulmonary TB patients under anti-TB treatment exhibit elevated DNA damage in peripheral blood mononuclear cells. This damage was not related to nitric oxide but may be due to other free radicals.

The role of oxidative stress on the pathophysiology of metabolic syndrome

Metabolic syndrome (MetS) has a high prevalence around the world. Considering the components used to classify MetS, it is clear that it is closely related to obesity. These two conditions begin with an increase in abdominal adipose tissue, which is metabolically more active, containing a greater amount of resident macrophages compared to other fat deposits. Abdominal adiposity promotes inflammation and oxidative stress, which are precursors of various complications involving MetS components, namely insulin resistance, hypertension and hyperlipidemia. One way to block the effects of oxidative stress would be through the antioxidant defense system, which offsets the excess free radicals. It is known that individuals with metabolic syndrome and obesity have high consumption of fats and sugars originated from processed foods containing high levels of sodium as well as low intake of fruits and vegetables, thus maintaining a state of oxidative stress, that can speed up the onset of MetS. Healthy eating habits could prevent or delay MetS by adding antioxidant-rich foods into the diet.

Increased production of hydrogen peroxide by peripheral blood monocytes associated with smoking exposure intensity in smokers

BackgroundSmoking is known to be associated with oxidative stress; however, it has not been elucidated whether the oxidative response is influenced by the intensity of smoking exposure.ObjectivesEvaluate the effect of smoking exposure on the secretion of hydrogen peroxide (H2O2) by the peripheral blood monocytes of smokers.MethodsA total of 25 smokers (50.3±8.8u2009years, 48% male) underwent the following evaluations: spirometry, pulse oximetry, body composition and total peripheral blood count. Peripheral blood monocyte (PBM) cultures were isolated and maintained, and IL-6 and TNF-α were measured in the plasma and in the supernatants of spontaneous and stimulated cultures. H2O2 was evaluated in the supernatants of the PBM cultures, and a subset of the PBM culture supernatants was stimulated with phorbol myristate acetate (PMA). We also evaluated 38 healthy controls (49.1±8.2u2009years, 42% male).ResultsThe spontaneous and stimulated monocytes’ secretion of H2O2 were statistically higher in the smokers than in the healthy controls (p<0.001). The H2O2 secretions were statistically significant higher after stimulation with PMA in both groups (p<0.001). In the multiple regression analysis, we identified a positive, statistically significant association between pack-years of smoking and the spontaneous secretion of H2O2 by PBM culture, adjusted for potential confounding variables. The association between PBM culture secretion of H2O2 and the production of TNF-α and IL-6 was not significant.ConclusionWe identified a positive association between higher production of H2O2 in smokers and higher smoking exposure during life. The influence of pack-years smoking may be a key modifiable factor in oxidative stress associated to smoking.