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Toxicologic Pathology
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Journal Article

Cytokine and Growth Factor Release by Alveolar Macrophages: Potential Biomarkers of Pulmonary Toxicity*1

Kevin E. Driscoll

The Procter & Gamble Company, Cincinnati, Ohio 45239-8707

James K. Maurer

The Procter & Gamble Company, Cincinnati, Ohio 45239-8707

Studies comparing pulmonary responses to crystalline silica (SiO2) and titanium dioxide (0.3 µm diameter, TiO2-F) demonstrated a positive correlation between alveolar macrophage (AM) release of interleukin-1 (IL-1), tumor necrosis factor (TNF) and fibronectin and, pulmonary granuloma formation, inflammation and fibrosis, respectively. AM IL-1 release was associated with the development of pulmonary granulomas after SiO2 exposure. AM release of TNF positively correlated with the degree of neutrophil recruitment after SiO 2 or TIO2-F exposure. A persistent increase in AM fibronectin release consistently correlated with the development of pulmonary fibrosis after SiO2 or TiO2-F exposure. Studies comparing pulmonary responses to ultrafine TiO2 (TiO2-D; particle diameter, 0.02 µm) with TiO2-F demonstrate that ultrafine particles have a relatively greater toxicity on a mass/lung basis. Exposure to TiO 2-D resulted in a persistent increase in AM TNF and fibronectin release which was associated with neutrophil recruitment and fibrosis, respectively. TiO2-D did not stimulate AM IL-1 release and this was consistent with the absence of a granulomatous response to TiO2-D. In light of the known bioactivities of IL-1, TNF and fibronectin, these correlative findings suggest that these mediators play significant roles in pulmonary responses to mineral dust exposure and may serve as potential early biomarkers of pulmonary toxicity.

Key Words: Alveolar macrophage • interleukin-1 • tumor necrosis factor • fibronectin • ultrafine particles • fibrosis • mineral dust • silica • titanium dioxide

Toxicologic Pathology, Vol. 19, No. 4-1, 398-405 (1991)
DOI: 10.1177/019262339101900408
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