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

Our plain-English summary of 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, by M. Comar, N. Zanotta, F. Zanconati, et al (Lung Cancer, 2016).

The study

• Authors: M. Comar, N. Zanotta, F. Zanconati, M. Cortale, A. Bonotti, A. Cristaudo, M. Bovenzi
• Journal: Lung Cancer
• Published: 2016;94:61-7
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: 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).

Materials And 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.

Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

In plain English

This cross-sectional study measured 12 immune signalling proteins (cytokines, chemokines and growth factors) in blood from 123 men with past work exposure to amphibole asbestos in dockyards and shipyards in the Provinces of Gorizia and Trieste, North-East Italy. This area has a high incidence of pleural malignant mesothelioma. Of the workers, 38 had no pleural or lung disorders, 46 had non-malignant asbestos diseases (pleural plaques, diffuse pleural thickening and/or pulmonary fibrosis), and 39 had pleural malignant mesothelioma. The comparison group was 33 healthy men with no occupational asbestos exposure. FGF-b, VEGF, RANTES, IP-10, CTACK, EOTAXIN and IL-5 were higher in the blood of each exposed group than in the comparison group. IL-6 was higher only in the mesothelioma group. Blood RANTES and IP-10 showed a significant trend with disease severity and rose significantly with longer exposure. In 16 mesothelioma patients, RANTES, VEGF and IP-10 were detectable in tumour tissue. Only RANTES showed a significant relation between blood and pleural fluid levels. The authors called the results preliminary. They concluded that RANTES may have a prognostic role in asbestos-related disease and said further studies are needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: cross-sectional study
• Who was studied: 123 male workers with definite occupational asbestos exposure, enrolled consecutively. Of these, 84 came from a health surveillance survey (38 free of pleural or lung disorders, 46 with non-malignant asbestos diseases) and 39 with pleural malignant mesothelioma came from a Thoracic Surgery Unit. The study area was the Provinces of Gorizia and Trieste, North-East Italy. There were also 33 healthy, non-smoking male controls with no occupational asbestos exposure. Enrolment dates are not given.
• Exposure: Past occupational exposure to amphibole asbestos in dockyards (asbestos handling and transport) and shipyards (naval construction and/or repair). Exposure duration was measured as years of employment in asbestos-related jobs. Median duration was 15 years for healthy workers, 19 for those with non-malignant disease and 25 for those with mesothelioma.
• Main results:
  • Serum levels of FGF-b, VEGF, RANTES, IP-10, CTACK, EOTAXIN and IL-5 were higher in the asbestos-exposed groups (healthy workers, workers with non-malignant disease, and workers with pleural mesothelioma) than in controls.
  • SCGF-b was significantly increased only in the healthy exposed workers and the workers with non-malignant asbestos diseases, not in the mesothelioma group. HGF, PDGF-b and TNF-alpha were not significantly increased in the mesothelioma group compared with controls.
  • IL-6 was significantly higher only in the workers with pleural mesothelioma, compared with controls and with the other two exposed groups.
  • Serum IP-10 and RANTES showed a positive, significant trend with severity of asbestos-related disease (p less than 0.001).
  • Median serum RANTES rose across groups: 4568 pg/mL in controls, 26132 pg/mL in healthy exposed workers, 26614 pg/mL in workers with non-malignant disease and 40489 pg/mL in workers with mesothelioma.
  • Among the 123 workers, median serum RANTES was 23436 pg/mL with 2 to 15 years of exposure (n = 35) and 52258 pg/mL with 27 to 37 years (n = 25); the test for trend gave p = 0.007. IP-10 also showed a significant trend with duration (p = 0.022). Only these two mediators increased significantly with exposure duration.
  • In 16 mesothelioma patients with matched samples, most mediators were higher in pleural fluid than in serum (p less than 0.001). PDGF-b showed the opposite. CTACK, RANTES, IL-5 and FGF-b showed no significant difference.
  • In mesothelioma biopsies from the 16 patients, RANTES (median 113 pg/mL), VEGF (109 pg/mL) and IP-10 (138 pg/mL) were detectable. The other mediators were excluded because more than 30% of samples were below the detection limit.
  • In the same 16 mesothelioma patients, only RANTES showed a significant relation between serum and pleural fluid concentrations.
  • The mesothelioma workers were older (median 69 years) and had longer occupational asbestos exposure (median 25 years) than the other worker groups (p less than 0.001).
• The authors' conclusion: The authors concluded that RANTES, because of its strong association with asbestos exposure, exposure duration and related clinical events, may have a prognostic role in the progression of asbestos-related diseases.
• Limitations the authors state:
  • The authors described their results as preliminary.
  • The authors stated that using RANTES as a biomarker for selecting people at risk of pleural mesothelioma needs further collaborative studies. These should include comparison with routinely used clinical parameters and with mesothelin.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Asbestos Exposure, Inflammation, Angiogenesis, Mesothelioma, Fibroblast, Occupational Exposure, Occupational History.

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• Increased levels of C-C chemokine RANTES in asbestos exposed workers and in malignant mesothelioma patients from an hyperendemic area — M. Comar, N. Zanotta, et al. (2014)
• Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development — T.A. Brown, A. Holian, et al. (2016)
• Epidemiology of malignant mesothelioma in Italy: surveillance systems, territorial clusters and occupations involved — A. Marinaccio, A. Binazzi, et al. (2018)
• Silica binds serum proteins resulting in a shift of the dose-response for silica-induced chemokine expression in an alveolar type II cell line — E.G. Barrett, C. Johnston, et al. (1999)
• Inflammatory Alteration of Human T Cells Exposed Continuously to Asbestos — N. Kumagai-Takei, S. Yamamoto, et al. (2018)

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