MMP-2 and MMP-9 activities and TIMP-1 and TIMP-2 expression in the prostatic tissue of two ethanol-preferring rat models.

We investigated whether chronic ethanol intake is capable of altering the MMP-2 and MMP-9 activities and TIMP-2 and TIMP-1 expression in the dorsal and lateral prostatic lobes of low (UChA) and high (UChB) ethanol-preferring rats. MMP-2 and MMP-9 activities and TIMP-1 and TIMP-2 expression were significantly reduced in the lateral prostatic lobe of the ethanol drinking animals. Dorsal prostatic lobe was less affected showing no significant alterations in these proteins, except for a reduction in the TIMP-1 expression in UChA rats. These important findings demonstrate that chronic ethanol intake impairs the physiological balance of the prostate extracellular matrix turnover, through downregulation of MMPs, which may contribute to the development of prostatic diseases. Furthermore, since these proteins are also components of prostate secretion, the negative impact of chronic ethanol intake on fertility may also involve reduction of MMPs and TIMPs in the seminal fluid.

Monocytes from pregnant women with pre-eclampsia are polarized to a M1 phenotype.

PROBLEM: This study evaluated whether the monocyte inflammatory state in pre-eclampsia (PE) might be associated with polarization to either M1 classically or M2 alternatively activated monocyte subsets. METHOD OF STUDY: Eighty-five women with (PE) and 52 normotensive (NT) pregnant women matched for gestational age were included. Expression of surface receptors characteristic of M1, such as Toll-like receptor (TLR)2, TLR4, and CD64, or M2, such as CD163 and CD206 monocyte subsets were evaluated in peripheral blood monocytes by flow cytometry. Tumour necrosis factor-alpha (TNF-α), interleukin-(IL)-12p40, IL-12p70, and IL-10 were evaluated in the supernatant of monocyte cultures by ELISA. RESULTS: Expression of TLR4 and CD64 by monocytes from pre-eclamptic women was significantly higher, while the expression of CD163 and CD206 expression was significantly lower compared with NT pregnant women. Endogenous production of TNF-α, IL-12p40, and IL-12p70 by monocytes was increased, while synthesis of IL-10 was lower in women with PE than in NT pregnant women. CONCLUSIONS: Monocytes from women with PE are classically activated, producing higher levels of pro-inflammatory cytokines, and express surface receptors characteristic of the M1 subset. These results provide evidence that the systemic inflammatory environment in PE may differentiate and polarize these cells to the M1 phenotype.

Metabolic syndrome risk factors in overweight, obese, and extremely obese Brazilian adolescents.

BACKGROUND: Obesity in infancy and adolescence has acquired epidemic dimensions worldwide and is considered a risk factor for a number of disorders that can manifest at an early age, such as Metabolic Syndrome (MS). In this study, we evaluated overweight, obese, and extremely obese adolescents for the presence of MS, and studied the prevalence of single factors of the syndrome in this population. METHODS: A total of 321 adolescents (174 females and 147 males) aged 10 to 16 years, attending the Adolescent Outpatient Clinic of Botucatu School of Medicine, Brazil, between April 2009 and April 2011 were enrolled in this study. Adolescents underwent anthropometric evaluation (weight, height, and abdominal circumference) and Body Mass Index (BMI) was estimated according to age and gender, following Disease Control and Prevention Centers recommendations (CDC, 2000). Blood pressure was measured and individuals with BMI ≥ 85th percentile were submitted to laboratory evaluation for Total Cholesterol, HDL and LDL Cholesterol, Triglycerides, Fasting Insulinemia, and Fasting Glycemia to identify MS factors, according to the criteria suggested by the International Diabetes Federation. Insulin resistance was calculated by HOMA-IR, Quicki, and Fasting Glycemia/Fasting Insulinemia (FGI). RESULTS AND DISCUSSION: Of the 321 adolescents, 95 (29.6%) were overweight, 129 (40.2%) were obese, and 97 (30.2%) were extremely obese. Around 18% were diagnosed with MS. The most prevalent risk factors were abdominal circumference ≥90th percentile (55%), HDL < 40 mg/dL (35.5%), High Pressure ≥130/85 mm/Hg (21%), Triglycerides ≥150 mg/dL (18.5%), and Fasting Glycemia ≥100 mg/dL (2%). Insulin resistance was observed in 65% of the adolescents. CONCLUSION: An increased prevalence of overweight and obesity, together with cardiometabolic risk factors such as dyslipidemia and abnormal blood pressure, were observed in adolescents, contributing to the onset of metabolic syndrome at younger ages. Risk factors for MS were more prevalent in females.

Chronic ethanol consumption alters all-trans-retinoic acid concentration and expression of their receptors on the prostate: a possible link between alcoholism and prostate damage.

BACKGROUND: Ethanol (EtOH) alters the all-trans-retinoic acid (ATRA) levels in some tissues. Retinol and ATRA are essential for cell proliferation, differentiation, and maintenance of prostate homeostasis. It has been suggested that disturbances in retinol/ATRA concentration as well as in the expression of retinoic acid receptors (RARs) contribute to benign prostate hyperplasia and prostate cancer. This study aimed to evaluate whether EtOH consumption is able to alter retinol and ATRA levels in the plasma and prostate tissue as well as the expression of RARs, cell proliferation, and apoptosis index. METHODS: All animals were divided into 4 groups (n = 10/group). UChA: rats fed 10% (v/v) EtOH ad libitum; UChACo: EtOH-naïve rats without access to EtOH; UChB: rats fed 10% (v/v) EtOH ad libitum; UChBCo: EtOH-naïve rats without access to EtOH. Animals were euthanized by decapitation after 60 days of EtOH consumption for high-performance liquid chromatography and light microscopy analysis. RESULTS: EtOH reduced plasma retinol concentration in both UChA and UChB groups, while the retinol concentration was not significantly different in prostate tissue. Conversely, plasma and prostate ATRA levels increased in UChB group compared with controls, beyond the up-regulation of RARß and -γ in dorsal prostate lobe. Additionally, no alteration was found in cell proliferation and apoptosis index involving dorsal and lateral prostate lobe. CONCLUSIONS: We conclude that EtOH alters the plasma retinol concentrations proportionally to the amount of EtOH consumed. Moreover, high EtOH consumption increases the concentration of ATRA in plasma/prostate tissue and especially induces the RARß and RARγ in the dorsal prostate lobe. EtOH consumption and increased ATRA levels were not associated with cell proliferation and apoptosis in the prostate.

Effects of inhaled nitric oxide on oxidative stress and histopathological and inflammatory lung injury in a saline-lavaged rabbit model of acute lung injury.

BACKGROUND: Conventional mechanical ventilation (CMV) is fundamental in acute respiratory distress syndrome (ARDS) treatment. Inhaled nitric oxide (INO), an adjunctive therapy, has been used with ventilation in an attempt to improve oxygenation and reduce lung injury. OBJECTIVE: To analyze the early effects of low INO dose on oxygenation, oxidative stress, inflammatory, and histopathological lung injury in a rabbit model of acute lung injury (ALI). METHODS: This was a prospective, controlled, in vivo animal laboratory study. Forty rabbits were instrumented and ventilated at F(IO(2)) 1.0. ALI was induced by tracheal infusion of warm saline (30 mL/kg, 38°C) and lung oxidative stress was assessed by total antioxidant performance (TAP) assay. Animals were assigned to groups: control group (no. = 10, low tidal volume [V(T)] = 6 mL/kg, PEEP = 5 cm H(2)O), ALI without INO (no-INO group, no. = 10, low V(T) = 6 mL/kg, PEEP = 10 cm H(2)O), ALI plus INO (INO group, no. = 10, low V(T) = 6 mL/kg, PEEP = 10 cm H(2)O, INO = 5 ppm). Plateau pressure was limited to 30 cm H(2)O in all groups. Ten non-instrumented animals (healthy group) were studied for TAP assay. Ventilatory and hemodynamic parameters were recorded every 30 min for 4 hours. RESULTS: After lung injury, the instrumented groups were worse than the control group for P(aO(2)) (control group 438 ± 87 mm Hg, no-INO group 80 ± 13 mm Hg, INO group 81 ± 24 mm Hg, P < .001). The INO group showed decreased lung inflammation by leukocyte count in lung lavage fluid (no-INO group 4.8 ± 1.64, control group 0.16 ± 0.15, INO group 0.96 ± 0.35 polymorphonuclear cells × 10(6)/bronchoalveolar lavage fluid/lung, P < .001), decreased histopathological injury score (no-INO group 5 [range 1-16], INO group 2 [range 0-5], control group 0 [range 0-3], P < .001), and better lung protection against oxidative injury than the no-INO group (healthy group 68 ± 8.7, control group 66.4 ± 6.8, INO group 56.3 ± 5.1, no-INO group 45.9 ± 3.4 percent protection/g protein, P < .001). CONCLUSIONS: INO attenuates oxidative stress and histopathological and inflammatory lung injury in a saline-lavaged rabbit ALI model.

Impact of skeletal maturation on bone metabolism biomarkers and bone mineral density in healthy Brazilian male adolescents.

OBJECTIVE: To evaluate the behavior of biomarkers of bone formation and resorption in healthy male Brazilian adolescents according to their biological maturation. METHODS: Eighty-seven volunteers were divided into age groups according to bone age (BA): 10-12 years (n = 25), 13-15 years (n = 36), and 16-18 years (n = 26). Weight (kg), height (m), body mass index (kg/m(2)), calcium intake from 3 days assessed by 24-h food recall (mg/day), pubertal event evaluation by Tanner criteria, and serum biomarker levels (osteocalcin [OC] [ng/mL], bone alkaline phosphatase [BAP] [U/L], and serum carboxyterminal telopeptide [S-CTx] [ng/mL]) were recorded and correlated to bone mineral density (BMD) (g/cm(2)) measured by dual energy X-ray absorptiometry of the lumbar spine, proximal femur, and whole body. RESULTS: Biomarkers showed similar behaviors, presenting higher median values in the 13-15 year group (BAP = 154.71 U/L, OC = 43.0 ng/mL, S-CTx = 2.09 ng/mL; p < 0.01) and when adolescents were in the pubertal stage G4. Median biomarker values decreased with advancing BA and sexual maturation. Biomarker values showed parallelism with peak height velocity, and, interestingly, bone formation biomarkers indicated significant negative correlation with BMD in the different evaluated locations, i.e., higher BMD values correlated with lower bone biomarker values. CONCLUSIONS: This is the first study of healthy Brazilian adolescents with rigid and careful inclusion and exclusion criteria to assess the correlation of bone markers and BMD with biological maturation indicators. Our results can help understand bone turnover and monitor bone metabolism.

Impacto da maturação esquelética em biomarcadores do metabolismo ósseo e na densidade mineral óssea em adolescentes brasileiros saudáveis / Impact of skeletal maturation on bone metabolism biomarkers and bone mineral density in healthy Brazilian male adolescents

OBJETIVO: Avaliar o comportamento de biomarcadores de formação e reabsorção óssea em adolescentes brasileiros em função da sua maturação biológica. MÉTODOS: Oitenta e sete voluntários foram divididos em grupos segundo a idade óssea (IO): 10-12 anos (n = 25), 13-15 anos (n = 36) e 16-18 anos (n = 26). Foram analisados peso (kg), estatura (m), índice de massa corporal (kg/m2), ingestão de cálcio de 3 dias (mg/dia), avaliação dos eventos pubertários pelos critérios de Tanner, níveis dos biomarcadores [osteocalcina (OC) (ng/mL), fosfatase alcalina óssea (FAO) (U/L), telopeptídeo carboxiterminal sérico (S-CTx) (ng/mL)] e sua correlação com a densidade mineral óssea (DMO) (g/cm2) por atenuação de raios X de dupla energia da coluna lombar, do fêmur proximal e de corpo total. RESULTADOS: Os biomarcadores mostraram comportamento semelhante, apresentando medianas elevadas dos 13 aos 15 anos (FAO = 154,71 U/L, OC = 43,0 ng/mL, S-CTx = 2,09 ng/mL; p < 0,01) e no estágio puberal G4. As medianas decresceram com o avançar da IO e da maturação sexual. Os níveis dos biomarcadores mostraram paralelismo com pico de velocidade em estatura, e, curiosamente, os biomarcadores de formação indicaram correlação negativa com a DMO, isto é, valores de DMO elevados se correlacionaram com valores baixos dos biomarcadores. CONCLUSÕES: Este é o primeiro estudo em adolescentes brasileiros com critérios de inclusão e exclusão rígidos e cuidadosos a avaliar a correlação entre marcadores ósseos e DMO frente a indicadores da maturação biológica. Os resultados ajudam a compreender o turnover ósseo e o monitoramento do metabolismo ósseo.

OBJECTIVE: To evaluate the behavior of biomarkers of bone formation and resorption in healthy male Brazilian adolescents according to their biological maturation. METHODS: Eighty-seven volunteers were divided into age groups according to bone age (BA): 10-12 years (n = 25), 13-15 years (n = 36), and 16-18 years (n = 26). Weight (kg), height (m), body mass index (kg/m2), calcium intake from 3 days assessed by 24-h food recall (mg/day), pubertal event evaluation by Tanner criteria, and serum biomarker levels (osteocalcin [OC] [ng/mL], bone alkaline phosphatase [BAP] [U/L], and serum carboxyterminal telopeptide [S-CTx] [ng/mL]) were recorded and correlated to bone mineral density (BMD) (g/cm2) measured by dual energy X-ray absorptiometry of the lumbar spine, proximal femur, and whole body. RESULTS: Biomarkers showed similar behaviors, presenting higher median values in the 13-15 year group (BAP = 154.71 U/L, OC = 43.0 ng/mL, S-CTx = 2.09 ng/mL; p < 0.01) and when adolescents were in the pubertal stage G4. Median biomarker values decreased with advancing BA and sexual maturation. Biomarker values showed parallelism with peak height velocity, and, interestingly, bone formation biomarkers indicated significant negative correlation with BMD in the different evaluated locations, i.e., higher BMD values correlated with lower bone biomarker values. CONCLUSIONS: This is the first study of healthy Brazilian adolescents with rigid and careful inclusion and exclusion criteria to assess the correlation of bone markers and BMD with biological maturation indicators. Our results can help understand bone turnover and monitor bone metabolism.

Comparison between procalcitonin and C-reactive protein for early diagnosis of children with sepsis or septic shock.

OBJECTIVE AND DESIGN: The objective of the paper is to examine the behavior of C-reactive protein (CRP) and procalcitonin (PCT) in the first 12 h of admission and verify which performs better to differentiate children with septic conditions. SUBJECTS: Septic children aged between 28 days and 14 years were divided into sepsis (SG; n = 46) and septic shock (SSG; n = 41) groups. CRP and PCT were measured at admission (T0) and 12 h later (T12 h). PCT results were classed as: 0.5 ng/ml = sepsis unlikely; >or=0.5 to <2 = sepsis possible; >or=2 to <10 = systemic inflammation; >or=10 = septic shock. RESULTS: At T0, there was a higher frequency of SSG with PCT >10 compared to SG [SSG: 30 (73.1%) > SG: 14 (30.4%); P < 0.05]. Similar results were observed at T12 h. Pediatric Risk of Mortality I score was significantly higher for SSG patients with higher PCT than SG patients. CRP levels were not statistically different for groups and time points. CONCLUSIONS: PCT was better than CRP for diagnosing sepsis and septic shock, mainly at admission, and is related to disease severity.

Interleukin-6 and procalcitonin in children with sepsis and septic shock.

OBJECTIVES: To examine the behavior of interleukin-6 (IL-6) and procalcitonin (PCT) and verify whether they can be used to differentiate children with septic conditions. METHODS: Septic children aged between 28 days and 14 years, prospectively enrolled from 01/2004 to 12/2005, were divided into sepsis (SG; n=47) and septic shock (SSG; n=43) groups. IL-6 and PCT were measured at admission (T0) and 12h later (T12h). PCT results were classed as: 0.5 ng/mL=sepsis unlikely; > or =0.5 to <2=sepsis possible; > or =2 to <10=systemic inflammation; > or =10=septic shock. RESULTS: Ninety children were included. At T0, there was a higher frequency of SSG with higher PCT compared with SG [SSG: 30 (69.7%)>SG: 14 (29.8%); p<0.05]. Similar results were observed at T12h. PRISM was significantly higher for SSG patients with higher PCT than SG patients. At T0, IL-6 levels were higher in SSG [SSG: 213.10 (10.85-396.70)>SG: 63.21 (0.86-409.82); p=0.001], but not statistically different at T12h. IL-6 levels positively correlated with PRISM score in SSG patients at admission (p=0.001; r=0.86). CONCLUSION: PCT and IL-6 appear to be helpful in early assessment of pediatric sepsis, are of diagnostic value at admission, and are related to disease severity.

Procalcitonina em crianças com sepse e choque séptico / Procalcitonin in children with sepsis and septic shock

OBJETIVOS: Estudar o comportamento da procalcitonina e verificar se é capaz de diferenciar crianças com quadros sépticos. MÉTODOS: Crianças de 28 dias a 14 anos de idade, admitidas de 01/2004 a 12/2005 na unidade de tratamento intensivo pediátrica da UNESP com sepse ou choque séptico, foram incluídas prospectivamente. Dois grupos foram constituídos: grupo sepse (GS; n = 47) e grupo choque séptico (GCS; n = 43). Procalcitonina foi medida à admissão (T0) e depois de 12 h (T12h), e os resultados apresentados em classes: < 0,5 ng/mL = sepse improvável; > 0,5 a < 2 = sepse possível; > 2 a < 10 = inflamação sistêmica e > 10 = choque séptico. RESULTADOS: No T0, foi maior a freqüência de pacientes do GCS na classe mais alta de procalcitonina, comparada às crianças do GS [GCS: 30 (69,7 por cento) > GS: 14 (29,8 por cento); p < 0,05]. Para o GCS, a freqüência de pacientes que ocupou a classe mais elevada foi maior que a de pacientes em outras classes (> 10 = 69,7 por cento; > 2 a < 10 = 18,6 por cento; > 0,5 a < 2 = 11,6 por cento; < 0,5 = 0,0 por cento; p < 0,05). No T12h, o comportamento da procalcitonina foi semelhante ao T0. O escore pediatric risk of mortality (PRISM) dos pacientes do GCS na classe mais alta de procalcitonina foi mais elevado que o das crianças do GS [GCS: 35,15 (40,5-28,7) versus GS: 18,6 (21,4-10,2); p < 0,05]. CONCLUSÃO: Procalcitonina permite diferenciar sepse de choque séptico, pode auxiliar no diagnóstico de quadros sépticos em crianças e pode estar relacionada à gravidade dos pacientes.

OBJECTIVES: To study the behavior of procalcitonin and to verify whether it can be used to differentiate children with septic conditions. METHODS: Children were enrolled prospectively from among those aged 28 days to 14 years, admitted between January 2004 and December 2005 to the pediatric intensive care unit at Universidade Estadual Paulista UNESP with sepsis or septic shock. The children were classified as belonging to one of two groups: the sepsis group (SG; n = 47) and the septic shock group (SSG; n = 43). Procalcitonin was measured at admission (T0) and again 12 hours later (T12h), and the results classed as: < 0.5 ng/mL = sepsis unlikely; > 0.5 to < 2 = sepsis possible; > 2 to < 10 = systemic inflammation and > 10 = septic shock. RESULTS: At T0 there was a greater proportion of SSG patients than SG patients in the highest PCT class [SSG: 30 (69.7 percent) > SG: 14 (29.8 percent); p < 0.05]. The proportion of SSG patients in this highest PCT class was greater than in all other classes (> 10 = 69.7 percent; > 2 to < 10 = 18.6 percent; > 0.5 to < 2 = 11.6 percent; < 0.5 = 0.0 percent; p < 0.05). The behavior of procalcitonin at T12h was similar to at T0. The pediatric risk of mortality (PRISM) scores for the SSG patients in the highest procalcitonin class were more elevated than for children in the SG [SSG: 35.15 (40.5-28.7) vs. SG: 18.6 (21.4-10.2); p < 0.05]. CONCLUSIONS: Procalcitonin allows sepsis to be differentiated from septic shock, can be of aid when diagnosing septic conditions in children and may be related to severity.

Procalcitonin in children with sepsis and septic shock.

OBJECTIVE: To study the behavior of procalcitonin and to verify whether it can be used to differentiate children with septic conditions. METHOD: Children were enrolled prospectively from among those aged 28 days to 14 years, admitted between January 2004 and December 2005 to the pediatric intensive care unit at UNESP with sepsis or septic shock. The children were classified as belonging to one of two groups: the sepsis group (SG; n = 47) and the septic shock group (SSG; n = 43). Procalcitonin was measured at admission (T0) and again 12 hours later (T12h), and the results classed as: < 0.5 ng/mL = sepsis unlikely; >/= 0.5 to < 2 = sepsis possible; >/= 2 to < 10 = systemic inflammation and >/= 10 = septic shock. RESULTS: At T0 there was a greater proportion of SSG patients than SG patients in the highest PCT class [SSG: 30 (69.7%) > SG: 14 (29.8%); p < 0.05]. The proportion of SSG patients in this highest PCT class was greater than in all other classes (>/= 10 = 69.7%; >/= 2 to < 10 = 18.6%; >/= 0.5 to < 2 = 11.6%; < 0.5 = 0.0%; p < 0.05). The behavior of procalcitonin at T12h was similar to at T0. The pediatric risk of mortality (PRISM) scores for the SSG patients in the highest procalcitonin class were more elevated than for children in the SG [SSG: 35.15 (40.5-28.7) vs. SG: 18.6 (21.4-10.2); p < 0.05]. CONCLUSIONS: Procalcitonin allows sepsis to be differentiated from septic shock, can be of aid when diagnosing septic conditions in children and may be related to severity.

Virulence profile of ten Paracoccidioides brasiliensis isolates: association with morphologic and genetic patterns.

Ten isolates of Paracoccidioides brasiliensis were examined for differences in virulence in outbred mice intravenously inoculated with the fungus, associated with mycelial morphology, and genetic patterns measured by random amplified polymorphic DNA (RAPD). Virulence was evaluated by viable yeast cell recovery from lungs and demonstration of histopathologic lesions in different organs. The results showed that the isolates presented four virulence degrees: high virulence, intermediate, low and non-virulence. RAPD clustered the isolates studied in two main groups with 56% of genetic similarity. Strains with low virulence, Pb265 or the non-virulent, Pb192, showed glabrous/cerebriform morphology and high genetic similarity (98.7%) when compared to the other isolates studied. The same was observed with Bt79 and Bt83 that shared 96% genetic similarity, cottony colonies and high virulence. The RAPD technique could only discriminate P. brasiliensis isolates according to glabrous/cerebriform or cottony colonies, and also high from low virulence strains. Isolates with intermediate virulence such as Pb18, Pb18B6, Bt32 and Bt56 showed variability in their similarity coefficient suggesting that RAPD was able to detect genetic variability in this fungal species. Virulence profile of P. brasiliensis demonstrated that both mycelial morphologic extreme phenotypes may be associated with fungal virulence and their in vitro subculture time. Thus, RAPD technique analysis employed in association with virulence, morphologic and immunologic aspects might prove adequate to detect differences between P. brasiliensis isolates.

Virulence profile of ten Paracoccidioides brasiliensis isolates: Association with morphologic and genetic patterns

Dez isolados de P. brasiliensis foram avaliados em relação à patogenicidade por inoculação intravenosa em camundongos e associação com morfologia miceliana e padrão genético por amplificação genônica do DNA polimórfico (RAPD). A patogenicidade, avaliada por recuperação de fungos viáveis a partir de tecido pulmonar e por lesões histopatológicas em diferentes órgãos, mostrou que os isolados apresentaram quatro graus de virulência: alta virulência, virulência intermediária, baixa virulência e não virulência. A técnica de RAPD agrupou os isolados em dois grupos com 56% de similaridade genética. Amostras com baixa virulência Pb265 ou não virulência Pb192 apresentaram morfologia glabra/cerebriforme e alta similaridade genética (98,7%) quando comparadas com os outros isolados estudados. O mesmo foi observado com os isolados Bt79 e Bt83, que compartilharam 96% de semelhança genética, colônias cotonosas e alta virulência. Essa técnica pode discriminar apenas isolados com morfologia glabra da cotonosa e com alta e baixa virulência. Isolados com virulência intermediária como Pb18, Pb18B6, Bt32 e Bt54 mostraram variabilidade no coeficiente de similaridade, sugerindo que a técnica de RAPD permite mostrar variabilidade genética nessa espécie fúngica. O estudo do perfil de virulência das amostras de P. brasiliensis demonstrou que os dois fenótipos extremos de morfologia miceliana podem ser associados com a virulência do fungo e com o tempo de subcultivo in vitro. Assim, a análise de RAPD, utilizada em conjunto com aspectos de virulência, morfológicos e imunológicos pode ser considerada adequada para detectar diferenças entre isolados de P. brasiliensis.

Production of pro- and anti-inflammatory cytokines by monocytes from patients with paracoccidioidomycosis.

Monocytes and macrophages can produce a large repertoire of cytokines and participate in the pathogenesis of granulomatous diseases. We investigated the production of pro- and anti-inflammatory cytokines by monocytes from patients with active paracoccidioidomycosis. Peripheral blood monocytes from 37 patients and 29 healthy controls were cultivated with or without 10 microg/ml of lipopolysaccharide (LPS) for 18 h at 37 degrees C, and the cytokine levels were determined in the culture supernatants by enzyme immunoassay. The results showed that the endogenous levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8, IL-10 and transforming growth factor beta detected in the supernatant of patient monocytes cultivated without stimulus were significantly higher than those produced by healthy controls. These data demonstrated that monocytes from patients with active paracoccidioidomycosis produce high levels of cytokines with both inflammatory and anti-inflammatory activities. However, patient monocytes produced significantly lower TNF-alpha and IL-6 levels in response to LPS when compared to normal subjects, suggesting an impairment in their capacity to produce these cytokines after LPS stimulation. Concentrations of IL-1beta, IL-8 and IL-10 in cultures stimulated with LPS were higher in patients than in controls. These results suggest that an imbalance in the production of pro- and anti-inflammatory cytokines might be associated with the pathogenesis of paracoccidioidomycosis.