1,721,005 research outputs found
Effects of continuous or pulsed exposure to rifabutin and sparfloxacin on the intracellular growth of Staphylococcus aureus and Mycobacterium tuberculosis
No full textFrequency of Th1, Th2 and Th17 producing T lymphocytes in bronchoalveolar lavage of patients with systemic sclerosis.
No full textOBJECTIVE: The pathophysiology of the lung fibrotic process in systemic sclerosis (SSc) is not fully elucidated. Since this pattern represents the leading cause of death in SSc, the knowledge of its actual pathophysiology is basic to prevent and stage pulmonary damage. In this study, we aimed to further investigate the relationship between the functional profiles of bronchoalveolar lavage (BAL) T cells and the pulmonary manifestation of the disease.
METHODS: With this aim, we assessed the frequency of Th1, Th2 and Th17 producing T-lymphocytes and their effector cytokines in BAL of SSc patients without signs or symptoms of lung interstitial involvement (SScFib-) and with interstitial lung fibrosis (SScFib+). We also study as control groups: patients with usual interstitial pneumonia (UIP), patients with sarcoidosis and 9 healthy controls (NHCs).
RESULTS: SScFib- showed an increase in BAL Th1/Th2 balance compared to NHCs, which was even higher than that observed in sarcoidosis. SScFib+ showed a shift towards a lower Th1/Th2 ratio as compared to SScFib-. The frequency of Th17 BAL T cells did not change among study groups.
CONCLUSION: Our data confirm the Th1/Th2 imbalance hypothesis on the pathogenesis of interstitial fibrosis in SSc patients, and suggest a possible utility in the assessment of BAL Th1/Th2 ratio
Acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections in community-acquired pneumonia and exacerbations of COPD or asthma: therapeutic considerations
No full textRates of acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections were determined in 115 adults hospitalized for community-acquired pneumonia (CAP), purulent exacerbations of COPD and acute exacerbations of bronchial asthma, by means of serology and molecular methods. Results were compared with those obtained in a matched control group. Common respiratory pathogens were isolated by cultures in 22.5% and 22.2% of CAP and exacerbated COPD patients, respectively. Cultures from exacerbated asthma patients were always negative. Serological and molecular evidence of current C. pneumoniae infection was obtained in 10.0%, 8.9% and 3.3% of CAP, COPD and asthma cases. The corresponding rates of acute M. pneumoniae infection were 17.5%, 6.7% and 3.3%, respectively. Finally, no difference was found between typical and atypical pathogen rates. These findings highlight the importance of taking into account C. pneumoniae and M. pneumoniae infections in guiding the choice of empirical antibacterial treatment for CAP and purulent exacerbations of COPD
Virulence of Mycobacterium tuberculosis affects inteleukin-8, monocyte chemoattractant protein-1 and interleukin-10 production by human mononuclear phagocytes
No full textMicrobial virulence and cytokine-mediated immune responses to Mycobacterium tuberculosis infection are important determinants of the pathogenesis of human tuberculosis. To determine the interrelationship between mycobacterial virulence and cytokine induction, human monocytes and monocyte-derived macrophages were infected with attenuated (H37Ra) and virulent (H37Rv and CH306) strains of M. tuberculosis and the amount of proinflammatory [interleukin (IL)-8 and monocyte chemoattractant protein (MCP)- 1] and inhibitory (IL- 10) cytokines was measured in the culture supernatants by enzyme-linked immunosorbent assay (ELISA). Infection with live bacilli induced de novo synthesis of IL-8, MCP-1 and IL-10, since cytokine release was abolished when cells were preincubated with the protein synthesis inhibitor cycloheximide. A differential production of antiinflammatory and inhibitory cytokines was observed. The amount of IL-8 and MCP-1 release was inversely related to strain virulence, the attenuated H37Ra strain being more prone than virulent strains to induce secretion of chemokines. In contrast, virulent strains induced greater amounts of the inhibitory cytokine IL-10. Efficient upregulation of IL-10 synthesis, but not of chemokines, required infection of cells with live bacilli, since heat killing of organisms or challenge with soluble mycobacterial products completely abrogated the effect. Moreover, cells infected with virulent strains produced IL-10 even at a very low bacillus-to-cell ratio and secreted IL-10 continuously during the 96 h that followed infection. The results suggest that the degree of virulence affects host cell responses to M. tuberculosis infection. Continued production of IL-10 may be one of the means by which M. tuberculosis downregulates acute local inflammatory reactions, favoring the development of tuberculosis
Acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections in community-acquired pneumonia and exacerbations of COPD or asthma: therapeutic considerations
No full textRates of acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections were determined in 115 adults hospitalized for community-acquired pneumonia (CAP), purulent exacerbations of COPD and acute exacerbations of bronchial asthma, by means of serology and molecular methods. Results were compared with those obtained in a matched control group. Common respiratory pathogens were isolated by cultures in 22.5% and 22.2% of CAP and exacerbated COPD patients, respectively. Cultures from exacerbated asthma patients were always negative. Serological and molecular evidence of current C. pneumoniae infection was obtained in 10.0%, 8.9% and 3.3% of CAP, COPD and asthma cases. The corresponding rates of acute M. pneumoniae infection were 17.5%, 6.7% and 3.3%, respectively. Finally, no difference was found between typical and atypical pathogen rates. These findings highlight the importance of taking into account C. pneumoniae and M. pneumoniae infections in guiding the choice of empirical antibacterial treatment for CAP and purulent exacerbations of COPD
The assessment of IFN-gamma and its regulatory cytokines in the plasma and bronchoalveolar lavage fluid of patients with active pulmonary tuberculosis
No full textOBJECTIVES: To assess the role of IFN-gamma and its regulatory cytokines in active pulmonary tuberculosis (TB).
DESIGN: Cytokines were measured in the plasma of TB patients and healthy subjects with different risk for TB exposure. In addition, cytokine profile was assessed in the bronchoalveolar lavage fluid (BALf) of six TB patients and nine normal controls.
RESULTS: Circulating IFN-gamma, IL-10 and IL-18 were higher in TB patients than in control groups. Plasma IL-12 levels were extremely variable, and no difference was observed among study groups. An inverse correlation between plasma IFN-gamma and IL-10 levels was found in TB patients. Furthermore, circulating IL-18 correlated with IL-10 but not with IFN-gamma levels. Finally, IFN-gamma, IL-18 and IL-12 were increased in the BALf of TB patients, whereas no difference was observed in IL-10 levels.
CONCLUSIONS: In human TB, at least at certain disease stages, there is a differential compartmentalization of the IFN-gamma-regulatory factors IL-12 and IL-10, the former being concentrated in the lungs and the latter being present in peripheral circulation. In addition, our findings address more critically the role of IL-18 in the host response to tuberculosis infection in humans
Ex vivo evaluation of PPD-specific IFN-gamma or IL-5 secreting cells in the peripheral blood and lungs of patients with tuberculosis
No full textOBJECTIVES: To evaluate ex vivo purified protein derivative (PPD) specific Th1- and Th2-type functional responses in human tuberculosis (TB).
DESIGN: IFN-gamma and IL-5 secreting cells were measured by a computer-assisted ELISPOT assay in the peripheral blood of patients with pulmonary TB, in patients with other respiratory diseases (control patients) and in tuberculin skin test negative or positive healthy controls. Moreover, the number of IFN-gamma or IL-5 spots was assessed in the bronchoalveolar lavage (BAL) cells of five patients with advanced TB and lung inflammation.
RESULTS: The frequency of PPD-specific IFN-gamma secreting cells in TB patients was higher than in control patients and healthy subjects. Although the number of PPD-specific IL-5 spots was low, a trend towards a higher frequency was observed in the peripheral blood of TB patients. Patients with advanced TB and lung inflammation had an increased number of both PPD-specific IFN-gamma and IL-5 spots in BAL as compared to that in peripheral blood, but the IFN-gamma/IL-5 ratio was about two-fold lower.
CONCLUSIONS: In human TB, the host response in the periphery is driven by a specific Th1-type cytokine response, whereas in the lungs of patients with advanced disease and lung inflammation, polarisation towards a Th2-like bias is observed
Frequency of Th1, Th2 and Th17 producing T lymphocytes in bronchoalveolar lavage of patients with systemic sclerosis
No full textOBJECTIVE: The pathophysiology of the lung fibrotic process in systemic sclerosis (SSc) is not fully elucidated. Since this pattern represents the leading cause of death in SSc, the knowledge of its actual pathophysiology is basic to prevent and stage pulmonary damage. In this study, we aimed to further investigate the relationship between the functional profiles of bronchoalveolar lavage (BAL) T cells and the pulmonary manifestation of the disease.
METHODS: With this aim, we assessed the frequency of Th1, Th2 and Th17 producing T-lymphocytes and their effector cytokines in BAL of SSc patients without signs or symptoms of lung interstitial involvement (SScFib-) and with interstitial lung fibrosis (SScFib+). We also study as control groups: patients with usual interstitial pneumonia (UIP), patients with sarcoidosis and 9 healthy controls (NHCs).
RESULTS: SScFib- showed an increase in BAL Th1/Th2 balance compared to NHCs, which was even higher than that observed in sarcoidosis. SScFib+ showed a shift towards a lower Th1/Th2 ratio as compared to SScFib-. The frequency of Th17 BAL T cells did not change among study groups.
CONCLUSION: Our data confirm the Th1/Th2 imbalance hypothesis on the pathogenesis of interstitial fibrosis in SSc patients, and suggest a possible utility in the assessment of BAL Th1/Th2 ratio
The assessment of IFN-gamma and its regulatory cytokines in the plasma and bronchoalveolar lavage fluid of patients with active pulmonary tuberculosis
No full textOBJECTIVES: To assess the role of IFN-gamma and its regulatory cytokines in active pulmonary tuberculosis (TB).
DESIGN: Cytokines were measured in the plasma of TB patients and healthy subjects with different risk for TB exposure. In addition, cytokine profile was assessed in the bronchoalveolar lavage fluid (BALf) of six TB patients and nine normal controls.
RESULTS: Circulating IFN-gamma, IL-10 and IL-18 were higher in TB patients than in control groups. Plasma IL-12 levels were extremely variable, and no difference was observed among study groups. An inverse correlation between plasma IFN-gamma and IL-10 levels was found in TB patients. Furthermore, circulating IL-18 correlated with IL-10 but not with IFN-gamma levels. Finally, IFN-gamma, IL-18 and IL-12 were increased in the BALf of TB patients, whereas no difference was observed in IL-10 levels.
CONCLUSIONS: In human TB, at least at certain disease stages, there is a differential compartmentalization of the IFN-gamma-regulatory factors IL-12 and IL-10, the former being concentrated in the lungs and the latter being present in peripheral circulation. In addition, our findings address more critically the role of IL-18 in the host response to tuberculosis infection in humans
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