title: Chemokines involved in the early inflammatory response and in pro-tumoral activity in asbestos-exposed workers from an Italian coastal area with territorial clusters of pleural malignant mesothelioma.
abstract: OBJECTIVE
  Immune mediators are likely to be relevant for the biological response to asbestos exposure. The aim of this study was to investigate the association between immune mediators involved in inflammation, cell survival and angiogenesis, and asbestos-related diseases in workers from a coastal area of North-East Italy with a high incidence of pleural malignant mesothelioma (PMM).
  
  
  METHODS
  A selected custom set of 12 soluble mediators was evaluated with a Luminex platform in sera, pleural fluid and mesothelioma biopsies from 123 asbestos-exposed workers (38 free from pleural-pulmonary disorders, 46 with non-malignant asbestos diseases, 39 with PMM) and in sera from 33 healthy controls from the same territorial area.
  
  
  RESULTS
  Increased immune mediator concentrations were observed in the sera of the asbestos-exposed workers compared to controls for human fibroblast growth factor (FGF-b), vascular endothelial growth factor (VEGF), CCL5 (RANTES), CXCL10 (IP-10), CLEC11A (SCGF-b), CCL27 (CTACK), CCL11 (EOTAXIN), IL-5 and IL-6 (p<0.001). The chemokines IP-10 and RANTES were associated with the severity of asbestos-related diseases. In the workers with PMM, the immune proteins secreted by mesothelioma biopsies showed detectable levels of RANTES, VEGF, and IP-10. In the same workers with PMM, a significant relationship between serum and pleural fluid concentrations was found for RANTES alone.
  
  
  CONCLUSIONS
  Occupational exposure to asbestos seems to drive the production of specific growth factors dually involved in the early inflammatory response and in pro-tumoral activity before clinical evidence of related disorders, suggesting that their over-expression may precede the onset of asbestos-related diseases. These findings suggest that some chemokines may have a prognostic role in the progression of asbestos-related diseases and could be used for the health surveillance of either workers with an occupational history of asbestos exposure or patients affected by non-malignant asbestos-related diseases.
authors.affiliation: Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, Italy; Clinical Unit of Hygiene, Department of Medical Sciences, University of Trieste, Trieste, Italy. Electronic address: manola.comar@burlo.trieste.it.
authors.forename: M
authors.initials: M
authors.lastname: Comar
authors.affiliation: Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Zanotta
authors.affiliation: Clinical Unit of Pathological Anatomy and Histology, Department of Medical Sciences, University of Trieste, Trieste, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Zanconati
authors.affiliation: Clinical Unit of Thoracic Surgery, Trieste General Hospital, Trieste, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cortale
authors.affiliation: Division of Occupational & Preventive Medicine, University Hospital of Pisa, Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bonotti
authors.affiliation: Division of Occupational & Preventive Medicine, University Hospital of Pisa, Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cristaudo
authors.affiliation: Clinical Unit of Occupational Medicine, Department of Medical Sciences, University of Trieste, Trieste, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bovenzi
mesh_terms: D001194:Asbestos / Q000009:adverse effects*; D015415:Biomarkers; D018925:Chemokines / Q000378:metabolism*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D007558:Italy / Q000453:epidemiology; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D008654:Mesothelioma / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism*; D000086002:Mesothelioma, Malignant; D016273:Occupational Exposure / Q000009:adverse effects; D010997:Pleural Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D001194:Asbestos
keywords: Growth factors; Non-malignant asbestos diseases; Occupational exposure to asbestos; Pleural malignant mesothelioma