Cytokine regulation of lung fibroblast proliferation. Pulmonary and systemic changes in asbestos-induced pulmonary fibrosis

Our plain-English summary of Cytokine regulation of lung fibroblast proliferation. Pulmonary and systemic changes in asbestos-induced pulmonary fibrosis, by I. Lemaire, H. Beaudoin, C. Dubois (The American Review of Respiratory Disease, 1986).

The study

• Authors: I. Lemaire, H. Beaudoin, C. Dubois
• Journal: The American Review of Respiratory Disease
• Published: 1986;134(4):653-8
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A complex series of interactions between immunocompetent cells and fibroblasts exists. Because pulmonary fibrosis may result from an increased number of collagen-producing fibroblasts, we studied the production of fibroblast growth factors derived from alveolar macrophages (AM) and peripheral blood mononuclear leukocytes (PBML) during the development of asbestos-induced fibrosis. Three groups of rats received, respectively, a single intratracheal injection of saline (control), 5 mg of asbestos, and 10 mg of asbestos. Bronchoalveolar lavage (BAL) and PBML isolation were performed on each animal 1, 3, and 6 months after instillation. Differential cell analyses revealed no significant change in the BAL cell populations except for a small but significant increase in the proportion of lymphocytes in the 10-mg group at 1 month and in both asbestos groups at 3 months. Similar analyses of PBML revealed only a small reduction in total PBML in the 10-mg group at 6 months. Bronchoalveolar cells (98% AM) from control rats spontaneously released a fibroblast growth factor (FGF), whereas Con-A-stimulated PBML of the same animals produced fibroblast growth inhibitory activity (FGIF). One month after asbestos exposure, when fibrotic lesions were apparent, AM production of FGF was significantly enhanced, and such increase persisted for as long as 6 months. By contrast, no significant change in FGIF production by Con-A-stimulated PBML was seen at the 1-month interval. However, 3 months after exposure, there was a significant suppression of FGIF production by PBML from rats in the 10-mg group and at 6 months by PBML from rats in both asbestos groups.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

In this animal experiment, male Wistar rats received one windpipe injection of saline, 5 mg, or 10 mg of UICC Canadian chrysotile B asbestos and were studied 1, 3 and 6 months later. The authors tested whether fluid from lung-washing cells (mostly alveolar macrophages) and blood white cells affected growth of human lung fibroblasts, scar-forming cells. At 1 month, macrophage fluid from the 5 mg and 10 mg groups raised fibroblast DNA synthesis 3.2-fold and 3.5-fold over plain medium, versus 1.8-fold for saline-treated rats. The increase persisted at 3 and 6 months. Chemically stimulated blood cells from control rats slowed fibroblast growth. This was unchanged in asbestos-treated rats at 1 month. It was lost in the 10 mg group by 3 months and both asbestos groups by 6 months. The authors concluded the macrophage growth factor may contribute to developing lung fibrosis. They suggested the later loss of the blood-cell inhibitor may be a consequence or amplifier of fibrosis. They noted that, given the injection method, their data do not relate to very early reactions to low-level inhaled asbestos.

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: animal experiment (rat model of asbestos-induced lung fibrosis, with laboratory cell-culture assays)
• Who was studied: Male Wistar rats weighing 250 to 300 g from Charles River Canada, studied 1, 3 and 6 months after treatment, in a laboratory at the Universite de Sherbrooke, Quebec. Group sizes are given inconsistently: three groups of 6 rats, but 15 animals killed at each time point. Fibroblast assays used human embryonic lung fibroblasts (WI-38).
• Exposure: A single intratracheal injection of saline (control), 5 mg, or 10 mg of UICC Canadian chrysotile B asbestos
• Main results:
  • In control rats, alveolar macrophages released a factor that stimulated fibroblast growth. Con A-stimulated blood mononuclear cells released a factor that inhibited fibroblast growth (43 ± 2%).
  • At 1 month, macrophage fluid from the 5 mg and 10 mg asbestos groups gave stimulation indices of 3.2 and 3.5, compared with 1.8 for control animals. The stimulation index is a laboratory measure of fibroblast DNA synthesis (tritiated thymidine uptake) relative to fibroblasts in medium alone.
  • At 3 and 6 months, macrophage fluid from both asbestos groups still stimulated fibroblast growth more than fluid from saline-treated rats.
  • At 1 month, stimulated blood-cell fluid from the 5 mg and 10 mg groups inhibited fibroblast growth by 40% and 42%, compared with 42% for controls.
  • At 3 months, stimulated blood-cell fluid from the 10 mg group no longer inhibited fibroblast growth. At 6 months, fluid from both asbestos groups failed to inhibit it.
  • In lung-washing fluid, there was a small, transient increase in lymphocytes in the 10 mg group at 1 month and in both asbestos groups at 3 months. Total cells, corrected for lung weight, did not differ significantly from controls.
  • Lung weight increased significantly in asbestos-exposed rats, by 130 to 155% over that in control animals.
  • In blood, there was a small but significant decrease in total mononuclear cell counts in the 10 mg group at 6 months only.
• The authors' conclusion: The authors concluded that local production of the macrophage fibroblast growth factor may be a contributing factor in the development of lung fibrosis. They concluded that systemic suppression of the lymphocyte growth-inhibitory factor occurs at the later stage of the disease and may be a consequence or an amplifying factor of the fibrotic process.
• Limitations the authors state:
  • Because the asbestos was injected into the windpipe, the data do not relate to the very early lung reactions to low-level inhalation exposure in humans and animals.
  • Inhalation exposure, which allows natural clearance of inhaled minerals, may affect the inflammatory cell response differently.
  • The study did not exclude an imbalance in the proportion of T-lymphocytes to B-lymphocytes.
  • Whether the lavage fluid itself contained fibroblast growth factors during the development of fibrosis is not known.

Topics

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

Medical terms in this study, explained in our Lexicon: Cytokine, Fibroblast, Pulmonary Fibrosis, Collagen, Alveolar Macrophage, Fibrosis, Bronchoalveolar Lavage (BAL), Asbestos Exposure.

Related studies

• Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)
• Immunoregulation of lung fibroblast growth: alteration in asbestos-induced pulmonary fibrosis — I. Lemaire, C. Dubois, et al. (1986)
• Changes in autacoid and neuropeptide contents of lung cells in asbestos-induced pulmonary fibrosis — R. Day, S. Lemaire, et al. (1987)
• Pulmonary reaction to long and short asbestos fibers is independent of fibroblast growth factor production by alveolar macrophages — I.Y. Adamson, D.H. Bowden (1990)
• 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)
• In vitro suppression of fibroblast growth inhibitory lymphokine production by asbestos — I. Lemaire, C. Dubois (1983)

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