Diesel exhaust particles stimulate the secretion of interleukin-1, but not tumor necrosis factor-alpha, in rat alveolar macrophages.
Exposure to diesel exhaust particles (DEP) in animals results in persistent lung inflammation. This study investigated the effects of DEP on release of proinflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-a), by rat alveolar macrophages (AM) in vitro. AM were isolated from male Sprague-Dawley rats (-300 g) and incubated with 0, 5, 10, 20, 50 or 100 ug DEP/10^6 AM/ml at 37 C in 5% CO2. Methanol was used to extract organic compounds from DEP. In concurrent experiments, the effects of washed DEP and methanol DEP extracts of equivalent concentrations were also tested. Twenty-four hours after exposure, AM supernatants were collected and IL-1 and TNF-a activities were determined, respectively, by a mouse thymocyte proliferation assay and a L929 cytotoxicity assay. Exposure to either DEP, washed DEP or methanol DEP extracts did not significantly affect AM viability, as indicated by the results of trypan blue exclusion and LDH release. DEP (at 50 and 100 ug) and methanol DEP extracts (at 20 and 100 ug) significantly increased IL-1 release from AM, while washed DEP was ineffective. In contrast, neither DEP, washed DEP nor methanol DEP extracts stimulated TNF-a production. These results show that DEP can directly activate rat AM to release IL- 1. This effect may be attributed to the organic components associated with DEP. Since DEP did not stimulate TNF-a production, IL-1 may play the more important role than TNF-a in DEP-induced inflammation.
The Toxicologist. Society of Toxicology 35th Annual Meeting, March 10-14,1996, Anaheim, California