interleukin-8 and Asbestosis

In the diagnosis of malignant mesothelioma (MM) there still is a lack of specific and sensitive screening biomarkers: this study examined the discriminatory power of a panel of serum/plasma biomarkers.. The study involved four groups: (a) individuals previously exposed to asbestos with asbestosis; (b) patients with MM; (c) patients with non-small cell lung cancer; and (d) controls without any evidence of malignancy. The concentrations of mesothelin, chitinase-3-like-1 (YKL-40), vascular endothelial growth factor (VEGF), endothelin-1, interleukin-8 (IL-8) and fibulin-3 in the serum of patients were determined.. Patients with MM had significantly higher serum levels of mesothelin (p<0.001), YKL-40 (p<0.001), IL-8 (p<0.001) and VEGF (p<0.01) than controls. The cut-off point for MM was 1.26 nM for mesothelin alone, and 167 pg/ml for YKL-40 alone; the presence of both markers above these cut-off levels improved diagnostic specificity.. The addition of YKL-40 may improve the specificity of mesothelin measurements alone for detecting patients with MM.

Topics: Adipokines; Aged; Asbestosis; Biomarkers, Tumor; Case-Control Studies; Chitinase-3-Like Protein 1; Cross-Sectional Studies; Endothelin-1; Female; GPI-Linked Proteins; Humans; Interleukin-8; Lectins; Lung Neoplasms; Male; Mesothelin; Mesothelioma; Middle Aged; Vascular Endothelial Growth Factor A

Asbestosis is associated with lung cellular and immunological abnormalities. Induced sputum cytology and local and systemic markers of inflammation may be helpful to characterize disease status and progression in these patients.. Thirty-nine ex-workers with asbestosis on high-resolution CT (HRCT) and 21 non-exposed controls were evaluated. Sputum cytology and IL-8 in serum and sputum were related to lung function impairment.. Subjects with asbestosis had reduced sputum cellularity but higher macrophage/neutrophil ratio and % macrophage as compared with controls. Sputum and serum IL-8 were also higher in patients with asbestosis (P < 0.05). In addition, evidence of lung architectural distorption on HRCT was associated with increased levels of serum IL-8. Interestingly, absolute macrophage number was negatively correlated with total lung capacity (r = -0.40; P = 0.04) and serum IL-8 to lung diffusing capacity (r = -0.45; P = 0.01).. Occupationally exposed subjects with asbestosis on HRCT have cytologic abnormalities in induced sputum and increased local and systemic pro-inflammatory status which are correlated to functional impairment.

Topics: Aged; Aged, 80 and over; Asbestosis; Brazil; Case-Control Studies; Humans; Interleukin-8; Interviews as Topic; Lung; Lung Volume Measurements; Male; Middle Aged; Spirometry; Sputum; Tomography, X-Ray Computed

Asbestosis is a fibrotic and inflammatory interstitial lung disease occurring after chronic occupational exposure to asbestos. An alveolitis has been described with activated alveolar macrophages and increased neutrophils as sampled by bronchoalveolar lavage (BAL). Animal models and in vitro studies demonstrate that asbestos can stimulate alveolar macrophages to release neutrophil chemotactic factor. We performed BAL on 18 nonsmoking individuals with asbestos exposure and observed a twofold increase in percent neutrophils recovered. Alveolar macrophages cultured in vitro from the asbestos-exposed individuals spontaneously released significant amounts of the neutrophil chemotaxin, interleukin-8 (IL-8). In addition, the alveolar macrophages expressed a 2.7-fold increase in steady state mRNA levels compared to unexposed normal controls utilizing the reverse transcriptase/polymerase chain reaction. In vitro experiments confirmed that crocidolite or chrysotile asbestos could stimulate the release of IL-8 from mononuclear phagocytes in a dose-dependent fashion. We conclude that asbestos exposure causes a mild neutrophilic alveolitis, and that IL-8 is one potential mediator capable of contributing to this inflammation in the lower respiratory tract.

Topics: Asbestos, Crocidolite; Asbestos, Serpentine; Asbestosis; Base Sequence; Humans; Interleukin-8; Macrophages, Alveolar; Molecular Sequence Data; RNA, Messenger

Alveolar neutrophil accumulation occurs in asbestosis. To evaluate a possible role for release of neutrophil chemotactic factor (NCF) in the pathogenesis of asbestosis, spontaneous NCF release from alveolar macrophages obtained by bronchoalveolar lavage (BAL) in eight individuals with asbestosis, 13 asbestos-exposed individuals without asbestosis, and five control subjects has been studied. Alveolar macrophages were incubated in medium (four hours; 37 degrees C), and neutrophil responses to the supernatants were assayed in a microchemotaxis chamber. Alveolar macrophages from subjects with asbestosis released more NCF (97 +/- 19 neutrophils per high-power field [N/HPF]) than controls (3 +/- 1 N/HPF; p less than 0.01). Alveolar macrophages from individuals with asbestos exposure and increased BAL neutrophil proportions (n = 7) released more NCF (93 +/- 24 N/HPF) than individuals with asbestos exposure and normal BAL neutrophil proportions (n = 6; 11 +/- 6 N/HPF; p less than 0.02). The results show that spontaneous NCF release occurs in asbestosis and that NCF release is associated with neutrophil alveolitis in asbestos-exposed individuals without asbestosis, suggesting a pathogenic role for NCF in mediating this neutrophil alveolitis. The results of the study also suggest that the presence of crackles is a better predictor of the presence of neutrophil alveolitis than is an abnormal chest x-ray film.

Topics: Asbestos; Asbestosis; Bronchoalveolar Lavage Fluid; Cell Count; Cells, Cultured; Chemotactic Factors; Environmental Exposure; Humans; Inflammation; Interleukin-8; Macrophages; Male; Middle Aged; Neutrophils; Pulmonary Alveoli