Asbestos and cancer: human natural killer cell activity is suppressed by asbestos fibers but can be restored by recombinant interleukin-2

Our plain-English summary of Asbestos and cancer: human natural killer cell activity is suppressed by asbestos fibers but can be restored by recombinant interleukin-2, by B.W. Robinson (The American Review of Respiratory Disease, 1989).

The study

• Author: B.W. Robinson
• Journal: The American Review of Respiratory Disease
• Published: 1989;139(4):897-901
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Inhalation of asbestos fibers is associated with a marked increase in the risk of developing pulmonary malignancy, particularly bronchogenic carcinoma. As natural killer (NK) cells are specialized lymphocytes that are considered to have an important in vivo role in the recognition and destruction of malignant cells, we examined the capacity of asbestos fibers (chrysotile, amosite, and crocidolite) to interfere with the NK activity of nylon wool-nonadherent, human blood lymphocytes (51Cr-release assay, K562 target cells, 14 h effector-to-target ratio = 50:1). Final asbestos concentrations used were 1 to 1,000 micrograms/ml. None of the fibers altered spontaneous target cell lysis or lymphocyte viability. All types of asbestos suppressed NK activity in a dose-dependent fashion. This effect was most marked with chrysotile, which exerted a profound inhibitory effect on blood NK cell activity; at 100 micrograms/ml, NK activity was inhibited 84 +/- 2% (p less than 0.001). The suppressive effects of asbestos were exerted directly on the NK cells (large granular lymphocytes, 91 +/- 2% inhibition at 100 micrograms/ml; p less than 0.001). Exposure of lymphocytes to recombinant interleukin-2 (IL-2, 150 units/ml) for 24 h prior to exposure to asbestos restored the level of activity to 99 +/- 6% of the original value (p less than 0.001), and lung lymphocytes that were exposed to IL-2 in vivo (active sarcoidosis) were resistant to suppression by asbestos. Similar results were observed in a group of patients with asbestosis. This suppression of NK activity may contribute to the increased susceptibility of asbestos-exposed persons to the development of pulmonary malignancy.

In plain English

This laboratory study tested whether asbestos fibers interfere with natural killer (NK) cells, immune cells thought to help destroy cancer cells. Blood lymphocytes from nine healthy laboratory workers were exposed to amosite, crocidolite or chrysotile at 1 to 1,000 micrograms per ml. Normal lung cells from four volunteers were tested with chrysotile. All three asbestos types suppressed blood NK activity in a dose-dependent way, most markedly intermediate-range chrysotile. At 100 micrograms per ml it inhibited NK activity 84 ± 2%, while short-range chrysotile caused 36 ± 6% suppression. The fibers did not reduce cell viability. Ceramic and glass wool fibers caused under 15% suppression. Treating cells with interleukin-2 (IL-2) for 24 hours before asbestos restored activity to 99 ± 6% of the original value. Lung lymphocytes from four patients with active sarcoidosis largely resisted suppression. Blood NK activity in nine people with asbestosis, all exposed to chrysotile, was similar to normal subjects. Lung cells from four of them were strongly suppressed by chrysotile in the laboratory. The authors concluded this suppression may contribute to asbestos-exposed persons' increased susceptibility to pulmonary malignancy.

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: Laboratory (in vitro) experiments on human blood and lung immune cells exposed to asbestos and other fibers
• Who was studied: Cells came from five groups: nine healthy laboratory workers (blood); four normal nonsmoking volunteers (lung, by bronchoalveolar lavage); nine asbestos-exposed persons with radiological pulmonary asbestosis (blood); four of those nine, who also gave lung cells; and four patients with active pulmonary sarcoidosis (lung). The work was done at the University Department of Medicine, Queen Elizabeth II Medical Centre, Nedlands, Western Australia.
• Exposure: Blood cells were exposed in the laboratory to three asbestos types at final concentrations of 1 to 1,000 micrograms per ml: amosite and crocidolite (IDCC reference samples) and chrysotile (NIEHS reference samples, intermediate-range and short-range). Lung cells were tested with chrysotile at 100 micrograms per ml. Ceramic wool and glass wool fibers were used for comparison. The asbestosis patients had all been exposed to chrysotile.
• Main results:
  • All three asbestos types suppressed normal blood NK cell activity in a dose-dependent fashion. The effect was most marked with intermediate-range chrysotile: at 100 micrograms per ml, NK activity was inhibited 84 ± 2% (p less than 0.001).
  • Short-range chrysotile also significantly suppressed blood NK activity, but less than intermediate-range chrysotile: 36 ± 6% suppression at 100 micrograms per ml (p less than 0.001 compared to normal saline).
  • Chrysotile acted directly on purified NK cells (large granular lymphocytes), with 91 ± 2% inhibition at 100 micrograms per ml (p less than 0.001).
  • The asbestos fibers did not reduce lymphocyte viability. The suppression was therefore a change in cell function, not cell killing.
  • Suppression required close contact between the fibers and the cells. When chrysotile fibers were removed after 1 hour, NK function recovered to 82 ± 5% of the original value.
  • Ceramic fibers and glass wool fibers caused little suppression at 1 to 1,000 micrograms per ml (less than 15% for both fiber types).
  • In normal blood cells, 24 hours of IL-2 raised NK activity to 66 ± 8%, compared with 38 ± 4% in medium alone. Adding asbestos afterwards still caused suppression, but activity in the IL-2-treated cells was restored to 99 ± 6% of the original value.
  • Lung lymphocytes from patients with active sarcoidosis were largely resistant to chrysotile at 100 micrograms per ml. Their cytotoxicity index was 21 ± 3% without asbestos and 20 ± 3% with it (p greater than 0.3).
  • In the asbestosis patients, blood NK activity was similar to that of normal subjects. Lung lymphocytes, which were obtained from four of these patients, behaved like normal lung cells. They showed a profound reduction in NK activity when exposed to chrysotile.
• The authors' conclusion: The authors concluded that asbestos-related suppression of NK activity may contribute to the increased susceptibility of asbestos-exposed persons to pulmonary malignancy. They also concluded that IL-2 can overcome the suppressive effects of asbestos fibers.
• Limitations the authors state:
  • The authors stated that the mechanisms behind the asbestos-related suppression of NK activity were not worked out in these studies.
  • The authors noted that serum in the assays may have helped keep the cells stable and reduced asbestos toxicity to the cells.

Topics

Medical terms in this study, explained in our Lexicon: Bronchogenic Carcinoma, Chrysotile, Amosite, Crocidolite.

Related studies

• Natural killer cell activity in asbestos workers. Interactive effects of smoking and asbestos exposure — R.D. deShazo, J. Morgan, et al. (1988)
• The Suppressed Induction of Human Mature Cytotoxic T Lymphocytes Caused by Asbestos Is Not due to Interleukin-2 Insufficiency — N. Kumagai-Takei, Y. Nishimura, et al. (2016)
• Safety, feasibility and therapeutic activity of intrapleural autologous lymphocyte conditioned medium followed by systemic recombinant interleukin-2 and interferon-alpha in a patient with malignant pleural mesothelioma — S. Duensing, H. Hamm, et al. (1997)
• NK cells from malignant pleural effusions are not anergic but produce cytokines and display strong antitumor activity on short-term IL-2 activation — P. Vacca, S. Martini, et al. (2013)
• Asbestos fibres inhibit the in vitro activity of lymphokine-activated killer (LAK) cells from healthy individuals and patients with malignant mesothelioma — L.S. Manning, M.R. Davis, et al. (1991)
• Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients — Y. Nishimura, N. Kumagai-Takei, et al. (2015)

Browse more research in The American Review of Respiratory Disease, or return to medical research.