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 ␤ (TGF-␤). 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 (glucocorticoidinduced tumor necrosis factor [TNF] receptor-related protein [GITR], CTLA-4, CD95L, LAP-1, and CD38). An analysis of regulatory activity showed that Treg cells from the AD group had greater activity than did cells from the other groups and that cell-cell contact is mandatory for this activity in the C group but was only partially involved in the regulatory activity of cells from AD patients. The addition of anti-IL-10 and anti-TGF-␤ neutralizing antibodies to the cultures showed that the production of cytokines may be another mechanism used by Treg cells. In conclusion, the elevated numbers of these cells with an increased regulatory phenotype and strong suppressive activity suggest a potential role for them in the immunosuppression characteristic of paracoccidioidomycosis. In addition, our results indicate that while Treg cells act by cell-cell contact, cytokine production also plays an important role.

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Study design: Cross-sectional. Objectives: Individuals with spinal cord injury (SCI) exhibit increased carotid intima-media thickness (IMT) and are reported to be exposed to higher circulating levels of inflammatory mediators. This study evaluated the relationship between inflammatory markers and carotid surrogates of cardiovascular risk in subjects with SCI. Setting: São Paulo, Brazil. Methods: A total of 65 nondiabetic, nonhypertensive, sedentary, nonsmoker men (34 with SCI; 31 healthy subjects) were evaluated by medical history, anthropometry, routine laboratory tests, analysis of hemodynamic, inflammatory parameters and ultrasound examination of carotid arteries. Results: Subjects with SCI (18 tetraplegic and 16 paraplegic) had lower systolic blood pressure (P ¼ 0.009), higher serum C-reactive protein (P ¼ 0.001), tumor necrosis factor (TNF) receptor-II (P ¼ 0.02) and TNF receptor-I (P ¼ 0.04) levels and increased in vitro production of interleukin-6 by mononuclear cells (P ¼ 0.04), compared to able-bodied individuals. No differences in serum interleukin-6, e-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and transforming growth factor-b levels, or in vitro release of interleukin-10, interleukin-17 and interferon-g by mononuclear cells, were detected between the studied groups. Common carotid IMT, but not internal carotid resistive index, was significantly higher in subjects with SCI (Po0.0001 adjusted for C-reactive protein and TNF receptor-II levels). In addition, tetraplegic subjects exhibited increased IMT (P ¼ 0.002 adjusted for systolic blood pressure and body mass index), but similar levels of inflammatory mediators compared to paraplegic ones. Conclusions: Individuals with SCI exhibit a clustering of vascular and inflammatory surrogates of increased cardiovascular risk. Nevertheless, subclinical carotid atherosclerosis is related to injury level but not to increased inflammatory status in these subjects.

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Chronic exercise training might partially reverse the inflammatory response caused by acute exercise in CAD patients. These results suggest that regular exercise is an important nonpharmacological strategy to the improvement in inflammation in CAD patients.

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.

ARTIGO ORIGINALAccuracy of white blood cell count, C-reactive protein, interleukin-6 and tumor necrosis factor alpha for diagnosing late neonatal sepsis Acurácia diagnóstica do leucograma, Resultados: Estudaram-se 82 crianças, sendo 42 no grupo SC, 16 no SP e 24 NI. Nos três momentos, as medianas da PCR e da IL-6 mostraram-se significativamente mais elevadas nos grupos SC e SP, e as do TNF-α alteraram-se apenas no grupo SC. Os índices diagnósticos da PCR foram elevados nos três momentos e com acurácia superior a do leucograma e semelhante a da IL-6 e a do TNF-α em suas primeiras medidas. Entre as citocinas, não houve diferença estatística entre elas, nem em relação ao leucograma. A associação dos testes não aumentou a capacidade diagnóstica, exceto na combinação entre leucograma e PCR2 e na dosagem seriada de PCR. Conclusões:A PCR e o leucograma mostram-se úteis no diagnóstico de sepse neonatal tardia e comparáveis à IL-6 e ao TNF-α. A acurácia aumentou com a associação PCR-leucograma e a dosagem seriada da PCR.J Pediatr (Rio J). 2008;84(6):536-542: Recém-nascido, sepse, proteína C-reativa, interleucina-6, fator de necrose tumoral, citocina, mediadores da inflamação. AbstractObjective: 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-α), in isolation and in conjunction.Methods: This was a diagnostic test validation study. Chemiluminescence was used to assay CRP, IL-6 and TNF-α 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. Patients were classified into three groups based on clinical progress and culture results: confirmed sepsis (CS), probable sepsis (PS), and not infected (NI). Statistical analysis was performed using the Wilcoxon and chi-square tests and Friedman analysis of variance; cutoffs were defined by plotting receiver operator characteristic curves. Results:The total study sample comprised 82 children, 42 of whom were classed as CS, 16 as PS and 24 as NI. At all three test times, the medians for CRP and IL-6 were significantly more elevated in the CS and PS groups, while the medians for TNF-α were abnormal only in the CS group. The CRP test had elevated indices of diagnostic utility at all three test times, better accuracy than the WBC and similar accuracy to the first IL-6 and TNF-α assays. There was no statistical difference between the cytokines, nor between them and the WBC. Combining tests did not increase diagnostic power, with the exception of the combination of WBC with CRP2 and when the sequential CRP assays were combined. Conclusions:Both CRP and WBC were useful for the diagnosis of late neonatal sepsis and comparable with IL-6 and TNF-α. Accuracy increased when CRP and WBC were combined and when sequential CRP assay results were used.J Pediatr (Rio J). 2008;84(6):536-542: Neonate, sepsis, C-reactive protein, interleukin-6, tumor necrosis factor, cytokine, inflammatory...