Human alveolar macrophage cytokine release in response to in vitro and in vivo asbestos exposure

Our plain-English summary of Human alveolar macrophage cytokine release in response to in vitro and in vivo asbestos exposure, by R.C. Perkins, R.K. Scheule, R. Hamilton, et al (Experimental Lung Research, 1993).

The study

• Authors: R.C. Perkins, R.K. Scheule, R. Hamilton, G. Gomes, G. Freidman, A. Holian
• Journal: Experimental Lung Research
• Published: 1993;19(1):55-65
• Cited by: 67 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The lung macrophage is proposed to be involved in the development of asbestos-induced pulmonary fibrosis. Knowledge of the effects of long-term asbestos exposure on lung macrophage cytokine release should better define the role of the macrophage in fibrogenesis. This study examines the effects of acute in vitro asbestos exposure and chronic in vivo asbestos exposure on human alveolar macrophage cytokine release. As indicators of asbestos-induced macrophage activation, the cellular release of IL-1 beta, TNF-alpha, IL-6, GM-CSF, and PGE2 was measured during a 24-h in vitro culture. Alveolar macrophages from normal volunteers were cultured in vitro with chrysotile asbestos. Of the factors measured, only TNF-alpha was elevated in response to asbestos exposure. Alveolar macrophages from asbestos-exposed individuals were placed into one of two groups based on their exposure history. These two groups were matched for age, smoking history, and diagnosis; none met the criteria for asbestosis. Cells isolated from subjects that had been exposed to asbestos for more than 10 years secreted enhanced basal amounts of IL-1 beta, TNF-alpha, IL-6, and PGE2, while those who had been exposed for less than 10 years did not. The results indicate that while asbestos had minimal acute effects on cytokine production by the human alveolar macrophage, intense, chronic exposure to asbestos leads to the enhanced basal release of significant amounts of several cytokines that have activity for the fibroblast, even in the absence of overt fibrosis.

In plain English

This laboratory study, from the University of Texas Medical School at Houston, measured cytokines (chemical signals) released by alveolar macrophages, immune cells washed out of the lungs during bronchoscopy. First, macrophages from healthy non-smoking volunteers were cultured for 24 hours with chrysotile asbestos. Of the factors measured (IL-1 beta, TNF-alpha, IL-6, GM-CSF and PGE2), only TNF-alpha rose significantly. Second, macrophages came from 11 clinic patients with past occupational asbestos exposure, none diagnosed with asbestosis, who were having bronchoscopy for medical reasons. They were grouped by work history: more than 10 years directly handling asbestos with visible dust, or under 10 years of possible exposure without handling it. Without added stimulation, cells from the longer-exposed group released significantly more IL-1 beta, TNF-alpha, IL-6 and PGE2 than the other group. GM-CSF was higher but not significantly so. The authors concluded that these raised levels could serve as an early marker of lung inflammation that may precede evident asbestosis. They noted that cells tested outside the body may not reflect their function in the lung, and that mild, undetectable fibrosis could not be excluded.

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 study of human lung cells: in vitro asbestos exposure of macrophages from normal volunteers, plus ex vivo comparison of macrophages from two groups of asbestos-exposed patients
• Who was studied: Asbestos-exposed patients evaluated in an occupational medicine clinic in Houston and undergoing bronchoscopy for medical reasons (such as a mass on X-ray or coughing blood), 11 in total split into group A and group B, none diagnosed with asbestosis. Also normal, non-smoking volunteers (N 6 for the in vitro experiment).
• Exposure: Group A (intense): more than 10 years in a job directly handling asbestos where dust was regularly visible, with no protective equipment. Group B (mild): under 10 years in an occupation with possible exposure, not involving handling asbestos. No subject had contact with asbestos for at least 8 years. In vitro: chrysotile asbestos (Calidria RG-144), with titanium dioxide as a control particle. The fiber type for the patients' work exposure is not stated.
• Main results:
  • Macrophages from normal volunteers exposed to chrysotile in vitro: only TNF-alpha was secreted significantly above basal levels. Titanium dioxide caused no change.
  • Unstimulated (basal) release: group A cells secreted significantly higher IL-1 beta, IL-6, TNF-alpha and PGE2 than group B cells (p less than 0.05). GM-CSF was elevated but did not reach significance.
  • Group A cytokine levels were generally one to two orders of magnitude greater than those from normal cells exposed to asbestos in vitro. Group B basal TNF-alpha and IL-6 were also significantly higher than those from in vitro exposed normal cells.
  • After stimulation with endotoxin (LPS), there were no statistically significant differences between groups A and B.
  • Ferruginous bodies were found in the lavage of all group A subjects and all but 2 group B subjects.
• The authors' conclusion: The authors concluded that the enhanced basal cytokine secretion by macrophages in asbestos-exposed subjects can be used as an early biomarker of an inflammatory lung response that may precede clinically evident asbestosis. They also concluded that the activation is consistent with a role for the macrophage in asbestos-related diseases.
• Limitations the authors state:
  • Cytokine release measured from cells outside the body may not exactly reflect macrophage function in the lung.
  • Mild fibrosis that current techniques cannot detect could not be ruled out in the subjects.
  • The roles of these cytokines in developing fibrosis would require long-term follow-up of a large population.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Santa Rita mine, Joaquin Ridge near Coalinga, California

All asbestos mines

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis.

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Cytokine, Asbestos Exposure, Macrophage, Pulmonary Fibrosis, PGE2, Chrysotile, Exposure History.

Related studies

• Distinctive profile of alveolar macrophage-derived cytokine release induced by fibrogenic and nonfibrogenic mineral dusts — I. Lemaire, S. Ouellet (1996)
• Asbestos stimulation triggers differential cytokine release from human monocytes and alveolar macrophages — L.J. Geist, L.S. Powers, et al. (2000)
• Cytokine and free radical responses of alveolar macrophages in vitro to asbestos fibres — L.C. Mongan, T. Jones, et al. (2000)
• Differential responses of murine alveolar macrophages to elongate mineral particles of asbestiform and non-asbestiform varieties: Cytotoxicity, cytokine secretion and transcriptional changes — T.O. Khaliullin, E.R. Kisin, et al. (2020)
• Refractory ceramic fibers activate alveolar macrophage eicosanoid and cytokine release — G.D. Leikauf, S.P. Fink, et al. (1995)
• Alveolar macrophage cytokine and growth factor production in a rat model of crocidolite-induced pulmonary inflammation and fibrosis — K.E. Driscoll, J.K. Maurer, et al. (1995)

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