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. Main endpoints were requirements for intra-aortic balloon pump, intensive care unit (ICU) stay longer than five days, ventilator dependence >24 h, requirement for dobutamine, hospital stay >10 days, clinical complications (infection, myocardial infarction, renal failure, stroke and ventricular arrhythmias) and in-hospital mortality. RESULTS: Preoperative BNP levels correlate with longer ICU stay (P = 0.003), longer ventilator use (P = 0.018) and duration of dobutamine use (P < 0.001). The receiver-operating characteristic curve demonstrated BNP levels >190 pg/ml as predictor of ICU >5 days and BNP levels >20.5 pg/ml correlated with dobutamine use, with areas under the curve of 0.712 and 0.842, respectively. Preoperative levels of ICAM-1 were associated with in-hospital mortality (P = 0.042). In the postoperative period, was found association between CRP, IL-6 and P-selectin with ventilation duration (P = 0.013, P = 0.006, P < 0.001, respectively) and P-selectin with ICU stay (P = 0.009). CONCLUSIONS: BNP correlates with clinical endpoints more than inflammatory markers and can be used as a predictor of early outcome after heart surgery.

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). Blood samples were collected before and 24 hours after surgery for determination of creatine kinase (CK)-MB (CK-MB), troponin I (cTnI), interleukin (IL)-6, IL-8, P-selectin, intercellular adhesion molecule (ICAM)-1 and C-reactive protein (CRP). Mortalities were registered at 12 months. RESULTS: Preoperative CK-MB and cTnI levels were 3.1 +/- 0.6 IU and 1.2 +/- 0.5 ng/mL for OffPCABG and 3.0 +/- 0.5 IU and 1.0 +/- 0.2 ng/mL for OnPCABG pts. Postoperative CK-MB and cTnI levels were 13.9 +/- 6.5 IU and 19.0 +/- 9.0 ng/mL for OffPCABG vs 29.5 +/- 11.0 IU and 31.5 +/- 10.1 ng/mL for OnPCABG (P < .01). OffPCABG and OnPCABG pts had similar preoperative IL-6 (10 +/- 7 and 9 +/- 13 pg/mL), IL-8 (19 +/- 7 and 17 +/- 7 pg/mL), soluble P-selectin (70 +/- 21 and 76 +/- 23 pg/mL), soluble ICAM-1 (117 +/- 50 and 127 +/- 52 ng/mL), and CRP (0.09 +/- 0.05 and 0.11 +/- 0.07 mg/L). At 24 hours, for OffPCABG and OnPCABG: IL-6 was 37 +/- 38 and 42 +/- 41 g/mL; IL-8, 33 +/- 31 and 60 +/- 15 pg/mL; soluble P-selectin, 99 +/- 26 and 172 +/- 30 pg/mL; soluble ICAM-1, 227 +/- 47 and 236 +/- 87 ng/mL; and CRP, 10 +/- 11 and 14 +/- 13 mg/L (P < .01 vs preoperation; P < .01 vs OffPCABG). Increased 24-hour postoperative CRP levels was the only marker to have significant positive correlations with events and occurred just for the OnPCABG pts. In-hospital and 1-year mortalities for the OnPCABG and OffPCABG pts were 2.0% and 2.2% (P = .1) and 2.7% and 4.7% (P = .06), respectively. CONCLUSIONS: Thus, the absence of CPB during CABG preserves better the myocardium and attenuates inflammation-however, without improving survival.

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. METHODS: Two groups of patients were primarily selected. The first group was comprised of diabetic outpatients with stable angina (D-CCS) and presence of coronary artery disease on coronary angiography (n=36). The second group was comprised of diabetic patients seen in the emergency room with acute coronary syndrome (D-ACS) without ST-segment elevation (n=38). Non-diabetic patients with ACS (n=22) and CCS (n=16) comprised the control group. Serum levels of CRP, IL-6 and IL-18 were determined using nephelometry (CRP) and ELISA (IL-6 and IL-18) techniques. RESULTS: Higher serum IL-6 levels were found in diabetic or non-diabetic patients with ACS than in the group with CCS. On the other hand, diabetic patients with ACS had higher CRP levels in comparison with the other groups. Serum IL-18 levels were not significantly different among the patients studied. CONCLUSION: our findings suggest a more intense inflammatory activity in patients with coronary instability. This inflammatory activity, as measured by CRP, seems to be even more intense in diabetic patients.

Níveis séricos de interleucina-6 (IL-6), interleucina-18 (IL-18) e proteína C reativa (PCR) na síndrome coronariana aguda sem supradesnivelamento do ST em pacientes com diabete tipo 2 / 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

FUNDAMENTO: A aterosclerose é uma doença inflamatória e níveis séricos de marcadores inflamatórios, como a interleucina 6 (IL-6), interleucina-18 (IL-18) e proteína C reativa (PCR), são utilizados para avaliação de pacientes em quadros de coronariopatia. No paciente com diabete do tipo 2, a aterosclerose está relacionada a um maior número de eventos como infarto e morte, quando comparado aos pacientes sem diabete. OBJETIVO: Avaliar a resposta inflamatória nos pacientes com diabete e eventos agudos de instabilidade coronariana. MÉTODOS: Selecionamos primariamente dois grupos de pacientes. O primeiro grupo foi composto por pacientes ambulatoriais diabéticos com angina estável (D-SCC) e presença de coronariopatia ao estudo coronariográfico (n = 36). O segundo grupo foi composto por pacientes diabéticos atendidos no pronto-socorro com quadro de síndrome coronariana aguda (D-SCA) sem supradesnivelamento do ST (n = 38). Como controle, foram utilizados pacientes sem diabete com SCA (n = 22) e SCC (n = 16). As concentrações séricas de PCR, IL-6 e IL-18 foram determinadas pelas técnicas de nefelometria (PCR) e ELISA (IL-6 e IL-18). RESULTADOS: Níveis mais elevados de IL-6 foram observados em pacientes com ou sem diabete e SCA em relação ao grupo com SCC. Por sua vez, pacientes com diabete e SCA apresentaram concentrações maiores de PCR em comparação aos outros grupos. Os níveis séricos de IL-18 não diferiram significativamente entre os pacientes estudados. CONCLUSÃO: Os resultados obtidos sugerem uma maior atividade inflamatória no paciente com quadro de instabilidade coronariana. Essa atividade inflamatória, medida pela PCR, parece ser ainda mais intensa no paciente com diabete.

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. METHODS: Two groups of patients were primarily selected. The first group was comprised of diabetic outpatients with stable angina (D-CCS) and presence of coronary artery disease on coronary angiography (n=36). The second group was comprised of diabetic patients seen in the emergency room with acute coronary syndrome (D-ACS) without ST-segment elevation (n=38). Non-diabetic patients with ACS (n=22) and CCS (n=16) comprised the control group. Serum levels of CRP, IL-6 and IL-18 were determined using nephelometry (CRP) and ELISA (IL-6 and IL-18) techniques. RESULTS: Higher serum IL-6 levels were found in diabetic or non-diabetic patients with ACS than in the group with CCS. On the other hand, diabetic patients with ACS had higher CRP levels in comparison with the other groups. Serum IL-18 levels were not significantly different among the patients studied. CONCLUSION: our findings suggest a more intense inflammatory activity in patients with coronary instability. This inflammatory activity, as measured by CRP, seems to be even more intense in diabetic patients.

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=0.036). Monocytes from SCD patients showed higher levels of p47(phox) phosphorylation compared with normal controls. INF-gamma release by lymphocytes from SCD patients was significantly higher compared with normal controls, after 48 h culture with phytohemagglutinin (P=0.02). The release of TNF-alpha by monocytes from SCD patients and normal controls was similar after 24 and 48 h culture with lipopolysaccharide (P>0.05). We conclude that monocytes from SCD patients show higher levels of gp91(phox) gene expression and p47(phox) phosphorylation, along with increased IFN-gamma release by SCD lymphocytes. These findings help to explain our previous observation showing the increased respiratory burst activity of mononuclear leukocytes from SCD patients and may contribute to inflammation and tissue damage in these patients.

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. In a double-blind, prospective, placebo-controlled study, 64 patients with ACS were randomized to receive pentoxifylline 400mg TID or placebo for 6 months. Analysis of the pro-inflammatory markers, C-reactive protein (CRP), interleukin (IL)-6, IL-12, interferon-gamma and tumor necrosis factor (TNF)-alpha and the anti-inflammatory cytokines, transforming growth factor (TGF)-beta1 and IL-10 were done at baseline, 1 and 6 months. Pentoxifylline treatment significantly reduced the adjusted levels of CRP and TNF-alpha compared to placebo after 6 months (P=0.04 and P<0.01, respectively). IL-12 increase was significantly less pronounced with pentoxifylline (P=0.04). The levels of the anti-inflammatory cytokine, IL-10, also declined significantly less in the pentoxifylline group compared to placebo (P<0.01) with a trend towards a higher increase of TGF-beta1 in the former group (P=0.16). Pentoxifylline reduces pro-inflammatory and increases anti-inflammatory response in patients with ACS and may have beneficial clinical effects on cardiovascular events.

Natural antibodies in paracoccidioidomycosis

Recente atenção tem sido dada aos anticorpos naturais como componentes da imunidade natural e como parte integrante da rede idiotípica. Todavia, seu papel funcional em diferentes infecções tem, raramente, sido estudado. O objetivo deste trabalho foi investigar a presença de anticorpos naturais na paracoccidioidomicose (PCM). Em adição, analisamos os anticorpos específicos anti-P. brasiliensis e sua distribuição em subclasses a fim de adquirir mais conhecimento sobre a resposta imune humoral nesta micose. Nossos achados mostram que a resposta de anticorpos naturais não é acentuada na PCM quando comparada com outras infecções por parasitas e, é restrita a poucas especificidades, sugerindo que o P. brasiliensis estimula moderadamente as células B CD5+. O anticorpo anti-actina foi a principal especificidade encontrada na PCM. Os anticorpos especificos para P. brasiliensis, nos pacientes crônicos, eram, principalmente, da subclasse IgG1.

Negative immunodiffusion test results obtained with sera of paracoccidioidomycosis patients may be related to low-avidity immunoglobulin G2 antibodies directed against carbohydrate epitopes.

Immunodiffusion (ID) is the serologic test most frequently used for the diagnosis and posttherapy follow-up of patients with paracoccidioidomycosis (PCM). The ID test is highly specific (100%), but its sensitivity is relatively low (90%), leading to false-negative results. The aim of this study was to determine the profiles of antibodies in sera from patients with proven PCM and with negative results in the ID test (IDneg) versus positive results in the ID test (IDpos). We analyzed 46 sera from patients with active PCM for total immunoglobulin G (IgG) and IgG subclass responses to Paracoccidioides brasiliensis gp43 antigen (treated or not treated with sodium metaperiodate) by enzyme-linked immunosorbent assay and immunoblotting. Immunoblotting showed that both IDneg and IDpos sera recognized predominantly the gp43 fraction of the P. brasiliensis antigen used in the ID test. IDneg sera contain low-avidity antibodies, low levels of specific IgG (total) and IgG1, and high levels of IgG2 compared with IDpos sera. The antibodies present in IDneg sera were predominantly directed against carbohydrate epitopes, since treatment with sodium metaperiodate resulted in a significant decrease in antibody reactivity. These data suggest that the lack of reactivity of sera from PCM patients in the ID test may be related to the production of low-avidity IgG2 antibodies directed against carbohydrate epitopes.

Cytokines and lymphocyte proliferation in juvenile and adult forms of paracoccidioidomycosis: comparison with infected and non-infected controls.

Cellular immune response to Paracoccidiodes brasiliensis antigens (PbAg) was evaluated in patients with the juvenile (JF) and adult (AF) forms of paracoccidioidomycosis as well as in a group of infected individuals living in the endemic area but without any clinical manifestation of the disease. The immune profile of this group of paracoccidioidomycosis-infected individuals was characterized by: 1) a positive skin test to P. brasiliensis antigen; 2) absence of specific antibodies; 3) a vigorous lymphoproliferative response to PbAg; and 4) a typical Th1 pattern of cytokines, with production of IFN-gamma and basal levels of IL-4, IL-5 and IL-10. At the opposite end of the spectrum were the JF patients whose proliferative response to PbAg was significantly impaired and whose cytokine pattern was characteristically Th2, i.e. lower IFN-gamma secretion and significantly higher levels of IL-4, IL-5 and IL-10. These profiles are compatible with forms of higher and lower resistance, respectively. Intermediate immune responses were observed in AF patients, whose specific lymphoproliferative response was lower than in the paracoccidioidomycosis-infected group but higher than in the JF patients. The secretion of IFN-gamma and IL-10 did not differ from the JF group, although IL-4 and IL-5 levels were significantly lower. Since AF patients are able to control fungal dissemination for decades, they can be considered more resistant than JF patients, who manifest the disease soon after infection.