A comparative dose-related response of several key pro- and antiinflammatory mediators in the lungs of rats, mice, and hamsters after subchronic inhalation of carbon black.

Objective: The objective of this study was to investigate mechanisms underlying species specificity in particle-induced lung inflammation.

Methods: Rats, mice, and hamsters exposed to air, 1, 7, or 50 mg/m3 of carbon black for 13 weeks were killed at 1 day, 3 months, and 11 months after exposure. Bronchoalveolar lavage was performed and characterized for cell number, cell type, reactive oxygen and nitrogen species, and cytokine levels. Ex vivo mutational analysis of inflammatory cells was evaluated by coincubating with lung epithelial cells. Lung tissue was evaluated for gene expression of various antiinflammatory mediators.

Results: There was a dose- and time-related effect with all the parameters. Rats demonstrated greater propensity for generating a proinflammatory response, whereas mice and hamsters demonstrated an increased antiinflammatory response.

Conclusions: These differences in pro- and antiinflammatory responses may contribute to the apparent species differences in inflammation and tumorigenesis.