Soluble triggering receptor expressed on myeloid cells in sputum of patients with community-acquired pneumonia or pulmonary tuberculosis: a pilot study.

Soluble triggering receptor expressed on myeloid cells (s-TREM-1) is upregulated on the surface of inflammatory cells in the presence of bacterial infections, apparently excluding those due to Mycobacterium tuberculosis. Therefore, sputum concentrations of s-TREM-1 may be of value in distinguishing bacterial pneumonia from pulmonary tuberculosis (PTB) in patients with respiratory infections. The current pilot study was designed to evaluate whether s-TREM-1 concentrations measured in the sputum of patients with suspected community-acquired pneumonia (CAP) allowed differentiation of those patients with PTB from other causes of pneumonia and to correlate s-TREM-1 with CURB-65, a marker of disease severity. Soluble s-TREM-1 concentrations were measured in sputum samples from patients admitted to a tertiary hospital with CAP or PTB by means of an ELISA procedure. Soluble-TREM-1 was readily detectable and quantifiable in sputum samples from patients with both CAP and PTB, with concentrations of 234±47 and 178±36 pg/ml respectively, but did not differ significantly between the two groups. However, patients with PTB had significantly lower leukocyte counts, 9±1.3 vs 15±1.4 × 10(9)/l compared with those without PTB. Interestingly, sputum s-TREM-1 concentrations correlated significantly with the CURB-65 pneumonia severity score calculated at the time of admission. Soluble-TREM-1 expression is upregulated in patients with both CAP and PTB, but does not differentiate between these two conditions. Sputum concentrations of s-TREM-1 may predict the severity of disease in patients with CAP.

Evaluation of circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) to predict risk profile, response to antimicrobial therapy, and development of complications in patients with chemotherapy-associated febrile neutropenia: a pilot study.

The soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) is a useful marker of infection in patients with sepsis, but has not been adequately evaluated in patients with chemotherapy-associated febrile neutropenia (FN). The value of sTREM-1 in this setting has been tested in a retrospective, pilot study using stored serum from 48 cancer patients with documented FN. On presentation, patients were categorized according to the Talcott risk-index clinical score. Circulating soluble sTREM-1 was measured using an ELISA procedure, while procalcitonin (PCT) or interleukins 6 (IL-6) and 8 (IL-8), included for comparison, were measured using an immunoluminescence-based assay and Bio-Plex® suspension bead array system, respectively. Circulating concentrations of both sTREM-1 and PCT were significantly (P < 0.05) elevated in patients at high risk for complications or death, as predicted by the Talcott score and were significantly lower in patients who responded to empiric antimicrobial agents. Neither IL-6 nor IL-8 accurately predicted serious complications in patients with FN. These observations, albeit from a pilot study, demonstrate that sTREM-1 is indeed elevated in high-risk patients with FN and is potentially useful to predict their clinical course, either together with, or as an alternative to PCT.

Prediction of outcome in cancer patients with febrile neutropenia: comparison of the Multinational Association of Supportive Care in Cancer risk-index score with procalcitonin, C-reactive protein, serum amyloid A, and interleukins-1beta, -6, -8 and -10.

The primary objective of the study was to compare the predictive potential of procalcitonin (PCT), C-reactive protein (CRP), serum amyloid A (SAA), and interleukin (IL)-1beta, IL-6, IL-8, and IL-10, with that of the Multinational Association of Supportive Care in Cancer (MASCC) risk-index score in cancer patients on presentation with chemotherapy-induced febrile neutropenia (FN). Seventy-eight consecutive FN episodes in 63 patients were included, and MASCC scores, as well as concentrations of CRP, SAA, PCT, and IL-1beta, IL-6, IL-8 and IL-10, and haematological parameters were determined on presentation, 72 h later and at outcome. Multivariate analysis of data revealed the MASCC score, but none of the laboratory parameters, to be an accurate, independent variable (P < 0.0001) for prediction of resolution with or without complications and death. Of the various laboratory parameters, PCT had the strongest association with the MASCC score (r = -0.51; P < 0.0001). In cancer patients who present with FN, the MASCC risk-index score is a useful predictor of outcome, while measurement of PCT, CRP, SAA, or IL-1beta, IL-6, IL-8 and IL-10, is of limited value.

Changes in mucosal and humoral atopic-related markers and immunoglobulins in elite cyclists participating in the Vuelta a España.

Atopic-related factors, humoral and mucosal immunoglobulins (Ig), and cortisol were measured in 17 professional cyclists competing in the 2003 Vuelta a España (a three-week multi-stage race). Venous blood and saliva samples were obtained the morning before the start of the race (T0), on the first rest day after 10 days of racing (T1), and before the start of the last stage after 21 days of racing (T2). Atopic-related factors, IgE, eosinophil cationic protein (ECP), and eosinophils, were significantly altered during the race. Serum IgE (T1: + 10 %) and ECP (salivary, T1: 113 % and serum, T2: 155 %) were significantly increased, while eosinophils (T1: - 32 %, T2: - 55 %) were significantly lower, than pre-race levels. Salivary sIgA secretion rate was significantly decreased at T2 (- 36 %). Pearson product-moment correlations revealed a modest correlation between salivary sIgA and salivary ECP (T1: r = 0.30; T2: r = 0.48; p < 0.01). Serum IgM, total IgG, IgG1, IgG2, IgA levels, at T1 and T2, and cortisol at T2, were significantly lower than pre-race levels. In conclusion, the elevation in IgE and ECP suggests an up-regulation of atopic-related factors in professional cyclists participating in the Vuelta a España. The correlation between salivary sIgA and salivary ECP indicates a role for sIgA in mediating mucosal inflammation. The alterations in Ig levels may indicate Ig isotype switching. An increasing state of hormonal fatigue may have influenced the observed immune alterations.

Pneumolysin-mediated activation of NFkappaB in human neutrophils is antagonized by docosahexaenoic acid.

This study was designed to investigate the relationship between influx of extracellular Ca(2+), activation of NFkappaB and synthesis of interleukin-8 (IL-8) following exposure of human neutrophils to subcytolytic concentrations (8.37 and 41.75 ng/ml) of the pneumococcal toxin, pneumolysin, as well as the potential of the omega-3 polyunsaturated fatty acid, docosahexaenoic acid, to antagonize these events. Activation and translocation of NFkappaB were measured using a radiometric electrophoretic mobility shift assay, while influx of extracellular Ca(2+) and synthesis of IL-8 were determined using a radioassay and an ELISA procedure, respectively. Exposure of neutrophils to pneumolysin was accompanied by influx of Ca(2+), activation of NFkappaB, and synthesis of IL-8, all of which were eliminated by inclusion of the Ca(2+)-chelating agent, EGTA (10 m m), in the cell-suspending medium, as well as by pretreatment of the cells with docosahexaenoic acid (5 and 10 microg/ml). The antagonistic effects of docosahexaenoic acid on these pro-inflammatory interactions of pneumolysin with neutrophils were not attributable to inactivation of the toxin, and required the continuous presence of the fatty acid. These observations demonstrate that activation of NFkappaB and synthesis of IL-8, following exposure of neutrophils to pneumolysin are dependent on toxin-mediated influx of Ca(2+) and that these potentially harmful activities of the toxin are antagonized by docosahexaenoic acid.

Antibodies to oxidised low-density lipoproteins and cardiolipin in pre-eclampsia and eclampsia.

The objective of this study was to test the hypothesis that autoantibodies to phospholipids and to oxidised low-density lipoprotein (ox-LDL) are increased in pre-eclamptic and eclamptic women compared with normal pregnancy. Serum concentrations of autoantibodies to ox-LDL and to cardiolipin were measured in 21 non-pregnant controls, 29 pregnant controls, 21 pre-eclamptic and six eclamptic women. Concentrations of IgG antibodies to ox-LDL and to cardiolipin were not significantly different in women with eclampsia as compared with the non-pregnant controls, pregnant controls and pre-eclampsia. Concentrations of IgM antibodies to cardiolipin were significantly lower in women with pre-eclampsia compared with non-pregnant controls and eclampsia. All three pregnant states differ markedly from the non-pregnant controls, of whom only 5% (1 of 21) had "high positive" IgG antibodies. These results suggest that ACAs rise as a result of the pregnant state rather than as a result of preeclampsia or eclampsia. According to these results, there is no evidence of increased production of serum autoantibodies against modified LDL in African women with pre-eclampsia, which may reflect reduced lipid peroxidation involving lipoproteins or no link at all. In addition, IgG and IgM anticardiolipin antibodies have no diagnostic value in preeclampsia and eclampsia.

Vitamin C supplementation attenuates the increases in circulating cortisol, adrenaline and anti-inflammatory polypeptides following ultramarathon running.

The effects of vitamin C supplementation on the alterations in the circulating concentrations of cortisol, adrenaline, interleukin-10 (IL-10) and interleukin-1 receptor antagonist (IL-1Ra) which accompany ultramarathon running were measured using immuno-chemiluminescence, radioimmunoassay and ELISA procedures. Forty-five participants in the 1999 Comrades 90 km marathon were divided into equal groups (n = 15) receiving 500 mg/day Vit C (VC-500), 1500 mg/day Vit C (VC-1500) or placebo (P) for 7 days before the race, on the day of the race, and for 2 days following completion. Runners recorded dietary intake before, during and after the race and provided 35 ml blood samples 15 - 18 hrs before the race, immediately post-race, 24 hrs post race and 48 hrs post-race. Twenty-nine runners (VC-1500, n = 12; VC-500, n = 10; P, n = 7) complied with all study requirements. All post-race concentrations were adjusted for plasma volume changes. Analyses of dietary intakes and blood glucose and anti-oxidant status on the day preceding the race and the day of the race did not reveal that carbohydrate intake or plasma vitamins E and A were significant confounders in the study. Mean pre-race concentrations of serum vitamin C in VC-500 and VC-1500 groups (128 +/- 31 and 153 +/- 34 micromol/l) were significantly higher than in the P group (83 +/- 39 micromol/l). Immediate post-race serum cortisol was significantly lower in the VC-1500 group (p < 0.05) than in P and VC-500 groups. When the data from VC-500 and P groups was combined (n = 17), immediate post-race plasma adrenaline, IL-10 and IL-1Ra concentrations were also significantly lower (p < 0.05) in the VC-1500 group. The study demonstrates an attenuation, albeit transient, of both the adrenal stress hormone and anti-inflammatory polypeptide response to prolonged exercise in runners who supplemented with 1500 mg vitamin C per day when compared to < or = 500 mg per day.

Systemic inflammatory indices in pre-eclampsia and eclampsia.

The objective of this study was to test the hypothesis that TNF-alpha, TNFp55 receptor and sICAM-1 are markers of immune activation, protective response to concentrations of TNF-alpha and endothelial cell activation, respectively, in pre-eclampsia. In addition, MPO and sL-selectin were selected as blood discriminators of neutrophil activation. This was a cross-sectional study comparing 21 non-pregnant controls, 29 normal pregnant controls, 21 pre-eclamptic and six eclamptic women. Blood concentrations of TNF-alpha, sTNFp55 receptor, sICAM-1, sL-selectin, myeloperoxidase, leucocyte count, neutrophil count, C-reactive protein and gamma-glutamyl transferase were estimated. The neutrophil count was significantly decreased in pre-eclampsia compared with normal pregnancy (9.12+/-0.95 vs. 12.52+/-0.80 x 10(9)/l, P<0.01). Serum concentrations of sL-selectin were significantly higher in non-pregnant controls compared with pregnant controls (P<0.0001), pre-eclampsia (P<0.0001) and eclampsia (P<0.0001). Serum concentrations of TNF-alpha, sTNFp55 receptor, sICAM-1, sL-selectin and MPO were not significantly different in women with pre-eclampsia compared with normal pregnancy. Serum concentrations of TNF-alpha, sTNFp55, sICAM-1, sL-selectin and MPO did not discriminate between normal and pre-eclamptic pregnancies. The high neutrophil count in normal and eclamptic pregnancies and the lack of shedded L-selectin suggests that neutrophil exudation to inflammatory sites was increased in women with an accompanying inflammatory response.

Influence of antimicrobial chemotherapy and smoking status on the plasma concentrations of vitamin C, vitamin E, beta-carotene, acute phase reactants, iron and lipid peroxides in patients with pulmonary tuberculosis.

SETTING: Inflammation-related oxidative stress has been implicated in the pathogenesis of lung fibrosis and dysfunction in patients with pulmonary tuberculosis. OBJECTIVE: To investigate the effects of antimicrobial chemotherapy and smoking status on the plasma concentrations of the anti-oxidative nutrients vitamin C, vitamin E and beta-carotene, as well as those of iron, lipid peroxides and the acute phase reactants C-reactive protein (CRP) and ferritin. DESIGN: A total of 41 patients with active pulmonary tuberculosis were studied at the outset and after 6 months of antimicrobial chemotherapy. RESULTS: Initial plasma concentrations of vitamin C and beta-carotene were low, returning to normal values after chemotherapy in the non-smokers, but not in the smokers, while those of vitamin E remained low throughout in both groups. Ferritin and CRP concentrations decreased significantly following chemotherapy, with the former higher in smokers than in non-smokers. Serum lipid peroxides were elevated in patients with pulmonary tuberculosis and were unaffected by chemotherapy or smoking habits, while iron levels were not significantly affected by chemotherapy. Although residual dysfunction and infiltration were evident, pulmonary function (FEV1) and radiographic score improved equally in both smokers and non-smokers following antimicrobial chemotherapy. CONCLUSIONS: Even after 6 months of apparently successful antimicrobial chemotherapy, pulmonary tuberculosis is associated with increased oxidative stress, which is unrelated to cigarette smoking and characterized by increased levels of circulating lipid peroxides and low concentrations of plasma vitamin E.

Increased levels of autoantibodies to cardiolipin and oxidised low density lipoprotein are inversely associated with plasma vitamin C status in cigarette smokers.

In this study we have measured circulating levels of autoantibodies to cardiolipin and oxidised low-density lipoprotein (ox-LDL) and correlated these with plasma concentrations of the anti-oxidant nutrients vitamin C, vitamin E and beta-carotene, in a group (79) of asymptomatic, male cigarette smokers and in non-smoking control subjects. Cigarette smoking, a well-known risk factor for development of atherosclerosis, was found to be associated with moderately elevated levels of autoantibodies to both cardiolipin and ox-LDL. Increased levels of these autoantibodies were most evident in the older smokers (> 30 years) and were significantly and inversely correlated with plasma vitamin C, but not with vitamin E or beta-carotene. Absorption studies designed to investigate the specificity of these autoantibodies demonstrated a high degree of cross-reactivity of cardiolipin antibodies with ox-LDL, while antibodies to the oxidatively modified lipoprotein tended to be specific for this antigen. These findings suggest that cigarette smoking promotes formation of autoantibodies to both cardiolipin and ox-LDL and that these may be involved in the initiation and/or perpetuation of atherosclerosis. Dietary intake of vitamin C may be a determinant of susceptibility to development of this cardiovascular disorder.