Anti-inflammatory cytokines in sickle cell disease.

Sickle cell disease (SCD) is a well-studied monogenetic disease with an established chronic inflammatory component. The paradigm shift towards inflammation has made the pathophysiology of SCD even more complex. Studies have shown that an imbalance between the pro-inflammatory and anti-inflammatory cytokines in SCD exists; however, the reports are skewed toward the pro-inflammatory mediators.

Near-fatal poisoning after ricin injection.

Objective: To report a near-fatal poisoning after intentional injection of ricin from a castor bean () extract.

Case Report: A 21 year-old man self-injected ∼3 mL of a castor bean extract intramuscularly and subcutaneously in the left antecubital fossa. Upon admission to our ED (1 h post-exposure; day 1, D1) he was awake and alert, but complained of mild local pain and showed slight local edema and erythema.

High levels of proinflammatory cytokines IL-6 and IL-8 are associated with a poor clinical outcome in sickle cell anemia.

Sickle cell anemia (SCA) pathophysiology is characterized by the activation of sickle red blood cells, reticulocytes, leukocytes, platelets, and endothelial cells, and with the expression of several inflammatory molecules. Therefore, it is conceivable that variations in levels of proinflammatory cytokines may act as a signaling of differential clinical course in SCA. Here, we evaluated the clinical impact of proinflammatory cytokines interleukin 1-β (IL-1β), interleukin 6 (IL-6), and interleukin 8 (IL-8) in 79 patients with SCA, followed in a single reference center from northeastern Brazil.

Characterization of CD4 T Cell Subsets in Patients with Abdominal Aortic Aneurysms.

Background: The mediators produced by CD4 T lymphocytes are involved in the pathogenesis of aneurysmal lesions in abdominal aortic aneurysm (AAA) patients. The aim of this study was to identify and characterize the CD4 T cell subsets involved in human AAA.

Methods: The CD4 T cell subsets in 30 human aneurysmal lesions were determined using flow cytometry (FC) and immunohistochemistry (IHC).

Functional and phenotypic evaluation of eosinophils from patients with the acute form of paracoccidioidomycosis.

Background: Eosinophilia is a typical finding of the acute/juvenile form of paracoccidioidomycosis (PCM), a systemic mycosis endemic in Latin America. This clinical form is characterized by depressed cellular immune response and production of Th2 cytokines. Moreover, it has been shown that the increased number of eosinophils in peripheral blood of patients returns to normal values after antifungal treatment.

Circulating levels of chemokines in psoriasis.

Chemokines may contribute to local and systemic inflammation in patients with psoriasis. Previous studies have demonstrated the importance of chemokine ligands and receptors in the recruitment of T cells into psoriatic lesional skin and synovial fluid. The aim of this study was to evaluate the levels of Th1-related chemokines in psoriasis and to investigate any association with disease severity.

Detection of TCD4+ subsets in human carotid atheroma.

Activated TCD4(+) cells are detected in human atherosclerotic plaques which indicate their participation in disease progression and destabilization. Among these cells, IFN-γ-producing T cells (TH1) are recognized as having a pro-atherogenic role. Recently, the IL-17-producing T helper lineage of cells (TH17) has been identified in atherosclerotic lesions.

Characterization of CD4+CD28null T cells in patients with coronary artery disease and individuals with risk factors for atherosclerosis.

Risk factors for atherosclerosis may contribute to chronic low-grade inflammation. A highly cytotoxic and inflammatory CD4(+) cell subset (CD4(+)CD28(null) cells) has been associated with inflammatory diseases, including acute coronary syndromes (ACS). The aim of this study was to quantify and characterize CD4(+)CD28(null) cells in individuals with risk factors for atherosclerosis and patients with coronary artery disease (CAD).

Phenotypic and functional characterization of NK cells in human immune response against the dimorphic fungus Paracoccidioides brasiliensis.

Besides their role in fighting viral infection and tumor resistance, recent studies have shown that NK cells also participate in the immune response against other infectious diseases. The aim of this study was to characterize the possible role of NK cells in the immune response against Paracoccidioides brasiliensis. Purified NK cells from paracoccidioidomycosis patients and healthy individuals were incubated with P.

Preoperative B-type natriuretic peptide, and not the inflammation status, predicts an adverse outcome for patients undergoing heart surgery.

Objectives: B-type natriuretic peptide (BNP) and inflammatory markers are implicated in the pathophysiology of both ischemic cardiomyopathy and complications after cardiac surgery with cardiopulmonary bypass (CPB). The purpose of this study was to assess preoperative and postoperative levels of BNP, interleukin-6 (IL-6), interleukin-8 (IL-8), P-selectin, intercellular adhesion molecule (ICAM), C-reactive protein (CRP) in patients undergoing cardiac surgery with CPB and investigate their variation and ability to correlate with immediate outcome.

Methods: Plasma levels of these markers were measured preoperatively, 6 and 24 h after CBP in 62 patients.

Involvement of regulatory T cells in the immunosuppression characteristic of patients with paracoccidioidomycosis.

Patients with paracoccidioidomycosis (PCM) exhibit a suppression of the cellular immune response characterized by negative delayed-type hypersensitivity (DTH) to Paracoccidioides brasiliensis antigens, the apoptosis of lymphocytes, and high levels of expression of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4), interleukin-10 (IL-10), and transforming growth factor β (TGF-β). The aim of this study was to investigate whether and how regulatory T cells (Treg cells) are involved in this immunosuppression by analyzing the number, phenotype, and activity of these cells in patients with active disease (AD group) and patients who had received treatment (TD group). Our results showed that the AD patients had more Treg cells than the TD patients or controls (C group) and also had elevated levels of expression of regulatory markers (glucocorticoid-induced tumor necrosis factor [TNF] receptor-related protein [GITR], CTLA-4, CD95L, LAP-1, and CD38).

TLR-2, TLR-4 and dectin-1 expression in human monocytes and neutrophils stimulated by Paracoccidioides brasiliensis.

Paracoccidioidomycosis (PCM) is an endemic mycosis in Latin America caused by the dimorphic fungus Paracoccidioides brasiliensis. The pattern of the immune responses to P. brasiliensis determines the disease progression and clinical outcome.

Reduced expression of systemic proinflammatory and myocardial biomarkers after off-pump versus on-pump coronary artery bypass surgery: a prospective randomized study.

Background: The effects of off-pump (OffPCABG) and on-pump (OnPCABG) coronary artery bypass grafting (CABG) on myocardium and inflammation are unclear.

Objective: Compare the inflammatory response and myocardial injury from patients (pts) submitted to OffPCABG with those that undergo OnPCABG.

Methods: Patients with normal left ventricular function were assigned to OffPCABG (n = 40) and OnPCABG (n = 41).

Accuracy of white blood cell count, C-reactive protein, interleukin-6 and tumor necrosis factor alpha for diagnosing late neonatal sepsis.

Objective: To evaluate the diagnostic value for late neonatal sepsis of white blood cell count (WBC) and assays for C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), in isolation and in conjunction.

Methods: This was a diagnostic test validation study. Chemiluminescence was used to assay CRP, IL-6 and TNF-alpha at the time of clinical suspicion and again after 24 and 48 hours, whereas the WBC was performed only once, at the time of suspicion.

The use of ultrafiltration for inflammatory mediators removal during cardiopulmonary bypass in coronary artery bypass graf surgery.

Objective: To investigate the effectiveness of ultrafiltration in removing inflammatory mediators released by cardiopulmonary bypass and to correlate ultrafiltration with alterations in organic function according to the Sequential Organ Failure Assessment Score.

Methods: Forty patients were included and randomized into two groups: "no ultrafiltration" (n=20; Group I) and "ultrafiltration" (n=20; Group II). Activated complement 3 and 4, interleukins 1beta, 6, 8 and tumor necrosis factor alfa were measured prior to anesthesia induction (Time 1), 5 minutes before cardiopulmonary bypass (Time 2), in the ultrafiltrated fluid (Time 3), 30 minutes (Time 4), and 6 (Time 5), 12 (Time 6), 24 (Time 7), 36 (Time 8) and 48 (Time 9) hours following cardiopulmonary bypass.

Systemic envenomation caused by the wandering spider Phoneutria nigriventer, with quantification of circulating venom.

Introduction: Bites by Phoneutria spp. spiders are common in Brazil, although only 0.5-1% result in severe envenomation, with most of these occurring in children.

Differences in the inflammatory response between patients with and those without diabetes mellitus after coronary stenting.

Background: Patients with diabetes mellitus who undergo coronary stenting are at increased risk of restenosis. It is known that inflammation plays a crucial role in restenosis.

Objective: We assessed the inflammatory response to elective coronary stent implantation (CSI) in stable diabetic and nondiabetic patients.

Differential expression of cytokines, chemokines and chemokine receptors in patients with coronary artery disease.

Monocytes/macrophages and lymphocytes have a key role in the pathogenesis of atherosclerosis through the production of inflammatory and anti-inflammatory cytokines. We evaluated mRNA expression and protein production of CCL2, CXCL8, CXCL9, CXCL10, IFN-gamma and IL-10 in vitro as well as the expression of the CCR2 and CXCR3 receptors in peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD) and healthy controls in the presence or absence of oxidized LDL (oxLDL). Patients with CAD showed higher constitutive expression of CCL2, CXCL8, CXCL9, CXCL10 and IFN-gamma mRNA and, after stimulation with oxLDL, higher expression of CCL2 and CXCL8 mRNA than the control group.

Serum levels of interleukin-6 (Il-6), interleukin-18 (Il-18) and C-reactive protein (CRP) in patients with type-2 diabetes and acute coronary syndrome without ST-segment elevation.

Background: Atherosclerosis is an inflammatory disease, and serum levels of inflammatory markers such as interleukin 6 (IL-6), interleukin 18 (IL-18) and C-reactive protein (CRP) are used to evaluate patients with coronary artery disease. In patients with type-2 diabetes, atherosclerosis is related to a larger number of events such as myocardial infarction and death, when compared with patients without diabetes.

Objective: To evaluate the inflammatory response in patients with diabetes and acute events of coronary instability.

Up-regulation of NADPH oxidase components and increased production of interferon-gamma by leukocytes from sickle cell disease patients.

We have previously demonstrated that mononuclear leukocytes from patients with sickle cell disease (SCD) release higher amounts of superoxide compared with normal controls. The aim of this study was to further study the NADPH oxidase system in these patients by investigating gene expression of NADPH oxidase components, phosphorylation of p47(phox) component, and the release of cytokines related to NADPH oxidase activation in mononuclear leukocytes from patients with SCD. gp91(phox) gene expression was significantly higher in monocytes from SCD patients compared with normal controls (P=0.

Pentoxifylline reduces pro-inflammatory and increases anti-inflammatory activity in patients with coronary artery disease--a randomized placebo-controlled study.

The balance between different immunological stimuli is essential in the progression and stabilization of atherosclerotic plaques. Immune regulation has been suggested as potential target for the treatment of atherosclerotic disease. We sought to determine whether treatment with pentoxifylline, a phosphodiesterase inhibitor with immunomodulating properties, could reduce the pro-inflammatory response observed in patients with acute coronary syndromes (ACS) and increase anti-inflammatory activity.

Regression of coronary artery outward remodeling in patients with non-ST-segment acute coronary syndromes: a longitudinal study using noninvasive magnetic resonance imaging.

Background: The association of plaques with outward arterial remodeling and acute coronary syndromes (ACS) has been mostly investigated by cross-sectional intravascular ultrasound studies. Magnetic resonance imaging (MRI) has made it possible to noninvasively assess the coronary vessels of patients with chronic coronary artery disease, but no study has been done in patients with ACS. We sought to serially investigate changes in coronary vessel walls of patients with ACS using noninvasive serial MRI.

Flow-cytometric analysis of cytokine production in human paracoccidioidomycosis.

Human infection with Paracoccidioides brasiliensis may result in three major outcomes: paracoccidioidomycosis-infection (PI), which is observed in healthy carriers living in endemic areas and the adult form (AF) and juvenile form (JF) of the disease. In this study we proposed to examine the intracellular expression of IFN-gamma, TNF-alpha, IL-2, IL-10, IL-12, CXCL8, CXCL9 and CXCL10 by peripheral blood mononuclear cells (PBMC) of patients with the JF and AF of the disease, as well as of PI individuals stimulated with PMA plus ionomycin, LPS or anti-CD3 plus anti-CD28, by flow cytometry. The results showed that PI individuals present a higher percentage of cells producing IFN-gamma, TNF-alpha, IL-2, CXCL9 and CXCL10 when compared to AF and JF patients.

Diagnosis of Paracoccidioidomycosis by detection of antigen and antibody in bronchoalveolar lavage fluids.

Paracoccidioidomycosis (PCM) is a systemic infection caused by the fungus Paracoccidioides brasiliensis and is believed to be the leading cause of fungal pulmonary infection. In this study, we used an inhibition enzyme-linked immunosorbent assay to diagnose pulmonary PCM based on the detection of 43-kDa and 70-kDa molecules in bronchoalveolar lavage fluids. The results were compared with results obtained by classical methods for antibody detection.

Kinetics of cytokines and chemokines gene expression distinguishes Paracoccidioides brasiliensis infection from disease.

The human infection with Paracoccidioides brasiliensis may result in three major outcomes: the paracoccidioidomycosis-infection (PI), the adult form (AF) and the juvenile form (JF) of the disease. The aim of this study was to compare the immunological response among these groups. The gene expression of multiple cytokines, including IL-4, IL-5, IL-6, IL-10, IFN-gamma, TNF-alpha and TGF-beta1, and chemokines, CXCL8, CXCL9 and CXCL10 was evaluated by RT-PCR in peripheral blood mononuclear cells unstimulated or following phytohemagglutinin stimulation for 3, 6, 12, 24 and 48 h.