The production of TNF-alpha and IL-1-like activity by bronchoalveolar leucocytes after intratracheal instillation of crocidolite asbestos

Our plain-English summary of The production of TNF-alpha and IL-1-like activity by bronchoalveolar leucocytes after intratracheal instillation of crocidolite asbestos, by X.Y. Li, D. Lamb, K. Donaldson (International Journal of Experimental Pathology, 1993).

The study

• Authors: X.Y. Li, D. Lamb, K. Donaldson
• Journal: International Journal of Experimental Pathology
• Published: 1993;74(4):403-10
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

We have used a rat intratracheal instillation model to study the effect of crocidolite asbestos exposure on cytokine production by bronchoalveolar lavage (BAL) leucocytes. In unexposed controls, the normal BAL leucocytes were mostly macrophages which spontaneously produced interleukin 1 (IL-1)-like activity and tumour necrosis factor (TNF-alpha) in culture; these levels were enhanced by stimulation with LPS. In animals exposed to crocidolite asbestos, two new types of cell, neutrophils and eosinophils, were recruited into the bronchoalveolar space by 1-3 days after instillation. However, the BAL profile had returned to normal by 14 days. The production of IL-1-like activity was decreased considerably compared to control from 1 to 14 days after asbestos instillation, but was increased at 30 days. However, the leucocytes produced increased TNF-alpha as early as 3 days after asbestos instillation and maintained this elevated level throughout the experimental period. Crocidolite asbestos in vitro also stimulated normal BAL leucocytes to release significantly increased amounts of IL-1-like activity and TNF-alpha. We conclude that the deposition of crocidolite asbestos fibre in the lung by instillation causes reduced production of IL-1-like activity in the acute phase, but elevated production of both IL-1-like activity and TNF in the chronic phase, suggesting that enhanced activities of these cytokines may contribute to the development of lung pathological changes in the long term.

In plain English

In this animal experiment, the authors instilled a standard sample of crocidolite asbestos into the windpipes of rats, then washed out their lungs at intervals up to one month. They counted the cell types recovered. They also measured how much of two inflammatory signalling substances, TNF-alpha and IL-1-like activity, those cells released in culture. After a 5 mg dose, neutrophils and eosinophils appeared at 1 to 3 days, and the cell mix was almost normal by 2 weeks. IL-1-like activity was reduced from day 1 to day 14 but rose above control levels at one month. TNF-alpha was higher than in controls at every time point except day 1. At one month, 1 mg and 5 mg doses raised TNF-alpha; 0.5 mg did not. Crocidolite added to normal lung cells in the dish doubled release of both substances. The authors noted that low-level endotoxin in culture media could have contributed to background release. They concluded that, in general, asbestos exposure increased production of both substances, with short-term variations after instillation.

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 intratracheal instillation with bronchoalveolar lavage), plus an in vitro cell experiment
• Who was studied: Wistar-derived rats of the HAN strain, male and female, 12-14 weeks old, from an animal centre in Edinburgh. There were 6-12 rats per group in the cell-count tables. No overall total is given.
• Exposure: UICC standard crocidolite asbestos. In the time-course experiment, rats received 5 mg instilled into the trachea and were examined at 1, 3, 14 and 30 days. In the dose experiment, rats received 0.5, 1 or 5 mg and were examined at one month. In the cell experiment, normal lung lavage cells were exposed to 50 micrograms per millilitre in vitro for 24 hours.
• Main results:
  • In normal (unexposed) rats, lavage cells were 99 (s.d. 0.7)% macrophages and 1 (s.d. 0.8)% lymphocytes, based on seven animals. These cells released IL-1-like activity and TNF-alpha in culture without added stimulation, and release increased with LPS stimulation.
  • After 5 mg crocidolite, the percentage of macrophages fell sharply at 1 day as neutrophils (PMN) increased, and eosinophils also appeared. Table 1 gives day-1 means of 64% macrophages, 26% neutrophils and 9% eosinophils, and 15% eosinophils at day 3. Macrophage percentage was almost fully restored by 2 weeks.
  • After 5 mg crocidolite, lavage cells released less IL-1-like activity than controls from day 1 to day 14. At one month, release rose above the level of control cells.
  • After 5 mg crocidolite, lavage cells released more TNF-alpha than controls at all time points except day 1.
  • At one month, IL-1-like activity showed a dose-related increase. TNF-alpha was increased after 1 mg or 5 mg in a dose-responsive manner, but not after 0.5 mg.
  • At one month, cell types were similar to controls across doses of 0.5 to 5 mg, except for a moderate increase in the percentage of neutrophils (PMN).
  • In vitro, adding crocidolite at 50 micrograms per millilitre doubled the spontaneous release of IL-1-like activity and TNF by normal lavage cells.
• The authors' conclusion: The authors concluded that, in general, lavage cells produced increased TNF and IL-1-like activity after both in vivo and in vitro asbestos exposure, with variations in the short term after in vivo exposure.
• Limitations the authors state:
  • Low-level endotoxin contamination of the culture media (up to 100 pg/ml) could have contributed to the spontaneous cytokine release.
  • The lower total cell count in the 5 mg group may reflect lavage difficulties or a toxic effect on cells.
  • How much neutrophils and eosinophils contributed to the cytokine levels is unknown.
  • The authors found the persistent fall in IL-1-like activity up to 14 days, alongside raised TNF-alpha, difficult to interpret.

Topics

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

Medical terms in this study, explained in our Lexicon: Crocidolite, Asbestos Exposure, Cytokine, Bronchoalveolar Lavage (BAL), Macrophage, Necrosis, Deposition.

Related studies

• Production of interleukin 1 by rat pleural leucocytes in culture after intratracheal instillation of crocidolite asbestos — X.Y. Li, D. Lamb, et al. (1993)
• Intratracheal injection of crocidolite asbestos depresses the secretion of tumor necrosis factor by pleural leukocytes in vitro — X.Y. Li, D. Lamb, et al. (1992)
• The ability of inflammatory bronchoalveolar leucocyte populations elicited with microbes or mineral dust to injure alveolar epithelial cells and degrade extracellular matrix in vitro — K. Donaldson, J. Slight, et al. (1988)
• Scanning electron microscopical investigations of broncho-alveolar casts after intratracheal asbestos fibre instillation — B. Voss, T. Kerenyi, et al. (2000)
• Increased 8-hydroxyguanine in DNA and its repair activity in hamster and rat lung after intratracheal instillation of crocidolite asbestos — R. Yamaguchi, T. Hirano, et al. (1999)
• Increased production of plasminogen activator inhibitor in vitro by pleural leukocytes from rats intratracheally instilled with crocidolite asbestos — X.Y. Li, G.M. Brown, et al. (1991)

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