Enhanced interleukin activity following asbestos inhalation

Our plain-English summary of Enhanced interleukin activity following asbestos inhalation, by D.P. Hartmann, M.M. Georgian, Y. Oghiso, et al (Clinical and Experimental Immunology, 1984).

The study

• Authors: D.P. Hartmann, M.M. Georgian, Y. Oghiso, E. Kagan
• Journal: Clinical and Experimental Immunology
• Published: 1984;55(3):643-50
• Cited by: 48 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Asbestos inhalation can cause pulmonary fibrosis and is associated with a variety of immunological abnormalities. The purpose of this study was to evaluate the effects of asbestos inhalation on interleukin-1 (IL-1) and interleukin-2 (IL-2) production in a rodent model. Two groups of rats were exposed, by intermittent inhalation, to either amphibole (crocidolite) or serpentine (chrysotile) asbestos. A third (control) group of rats was sham exposed to clean air. Animals from the three exposure groups were thereafter immunized (or not immunized) with fetal calf serum antigens. In order to assay interleukin activity, supernatants were generated from cultures containing alveolar macrophages and autologous splenic lymphocytes, and from cultures containing alveolar macrophages alone. Using assay systems designed to detect IL-1 and IL-2 functional activity, the supernatants were evaluated for their capacity to stimulate lymphoproliferation and fibroblast DNA synthesis. Macrophage-lymphocyte co-culture supernatants, when obtained from immunized, asbestos exposed rats, contained greater IL-1 and IL-2 activity than identical supernatants from immunized, sham exposed animals. These between group differences were not, however, observed in supernatants from unimmunized rats, or when supernatants were generated in the absence of immune lymphocytes. These observations suggest that asbestos exposure is associated with enhanced activation of lymphocytes by antigens. The possible relevance of these findings to asbestos related fibrogenesis and immunological stimulation is discussed.

In plain English

In this animal experiment, three groups of male inbred Fischer-344 rats breathed crocidolite asbestos, chrysotile asbestos, or clean air (sham exposure) intermittently over 91 days. About 15 to 20 months after exposure ended, rats were immunized with fetal calf serum proteins or given a comparison injection without them, and were killed 7 days later. The authors cultured lung macrophages, either with the same rat's spleen lymphocytes or alone, and tested the culture fluids for interleukin-1 and interleukin-2 activity (immune signaling molecules). In immunized rats, macrophage-lymphocyte fluids from both asbestos groups stimulated mouse thymocyte growth (p less than 0.05) and human fibroblast DNA synthesis significantly more than fluids from sham-exposed rats. The two fiber types did not differ significantly. Fluids from non-immunized rats caused negligible thymocyte stimulation. Macrophages cultured alone showed no between-group differences in the fibroblast test. The authors concluded that both fiber types were associated with enhanced antigen-directed release of factors with interleukin-1 and interleukin-2 activity, adding that these factors require further characterization.

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 (inhalation exposure of rats, followed by laboratory cell-culture assays)
• Who was studied: Male inbred Fischer-344 rats in three inhalation groups (crocidolite, chrysotile, sham). About 15-20 months after exposure ended, rats in each group were immunized with fetal calf serum, or were 'negative control' animals injected without it. All were sacrificed 7 days after sensitization. The number of rats per group is not stated; the figure legends refer to six experiments per group.
• Exposure: Intermittent inhalation over 91 days of UICC reference crocidolite asbestos or chrysotile asbestos from the Jeffrey Mine, Quebec (Johns-Manville). A control group was exposed to clean air only. The mean concentrations are printed with damaged decimal points in the scanned text.
• Main results:
  • In immunized rats, supernatants from macrophage-lymphocyte co-cultures of both asbestos-exposed groups induced significantly greater mouse thymocyte DNA synthesis than those from sham-exposed rats (p less than 0.05).
  • Thymocyte-stimulating activity was greater in chrysotile-exposed than in crocidolite-exposed rats, but this difference was not statistically significant (p greater than 0.05).
  • Co-culture supernatants from both asbestos-exposed groups also showed greater proliferative activity on CT-6 cells (an IL-2-dependent cell line) than those from sham-exposed rats. The data were not shown. The authors took this to suggest IL-2 activity.
  • Thymocyte-stimulating activity peaked at 48 hours of culture for supernatants from crocidolite- and chrysotile-exposed rats. At all time points it was greater in both asbestos groups than in the sham group.
  • Co-culture supernatants from immunized crocidolite- and chrysotile-exposed rats induced significantly greater human fibroblast DNA synthesis than those from sham-exposed rats. The P-value is printed in the scan as 'P<0 01', with its decimal point lost. The two asbestos groups did not differ significantly. The authors took this to suggest IL-1 activity.
  • Supernatants from macrophages cultured without lymphocytes stimulated fibroblast DNA synthesis in all three groups at a 1/4 dilution, with no between-group differences. At a 1/16 dilution they caused minimal uptake.
  • Co-culture supernatants from non-immunized ('negative control') rats in all three inhalation groups induced negligible thymocyte uptake of labelled thymidine.
• The authors' conclusion: The authors concluded that both amphibole (crocidolite) and serpentine (chrysotile) asbestos inhalation were associated with enhanced antigen-directed release of factors showing IL-1 and IL-2 activities. They postulated a possible dual role for these factors in asbestosis and in asbestos-related immunological stimulation.
• Limitations the authors state:
  • The substances detected were not definitively identified as interleukins; the authors state they require further characterization and purification.
  • The relevance of these laboratory findings to the living animal had not been established.
  • An artificial antigen (fetal calf serum) was used for immunization.

Mines named here

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

• Jeffrey mine, Asbestos, Quebec

All asbestos mines

Topics

Medical terms in this study, explained in our Lexicon: Pulmonary Fibrosis, Amphibole Group, Crocidolite, Serpentine Group, Chrysotile, Alveolar Macrophage, Fibroblast, Macrophage.

Related studies

• Interleukin 1 production and accessory cell function of rat alveolar macrophages exposed to mineral dust particles — Y. Oghiso, Y. Kubota (1987)
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• 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)
• Asbestos fibers and interleukin-1 upregulate the formation of reactive nitrogen species in rat pleural mesothelial cells — N. Choe, S. Tanaka, et al. (1998)
• Asbestos and cancer: human natural killer cell activity is suppressed by asbestos fibers but can be restored by recombinant interleukin-2 — B.W. Robinson (1989)
• Production of interleukin 1 by rat pleural leucocytes in culture after intratracheal instillation of crocidolite asbestos — X.Y. Li, D. Lamb, et al. (1993)

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