Toxic effect in the lungs of rats after inhalation exposure to benzalkonium chloride

Background: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) toxic to microorganisms. Inhalation is one of the major possible routes of human exposure to BAC. Materials and Methods: Experiments were performed on female Wistar rats. The rats were exposed to aerosol of BAC water solution at the target concentration of 0 (control group) and 35 mg/m3 for 5 days (6 h/day) and, after a 2-week interval, the animals were challenged (day 21) with BAC aerosol at the target concentration of 0 (control group) and 35 mg/m3 for 6 h. Results: Compared to the controls, the animals exposed to BAC aerosol were characterized by lower food intake and their body weight was significantly smaller. As regards BAC-exposed group, a significant increase was noted in relative lung mass, total protein concentration, and MIP-2 in BALF both directly after the termination of the exposure and 18 h afterwards. Significantly higher IL-6 and IgE concentrations in BALF and a decrease in the CC16 concentration in BALF were found in the exposed group immediately after the exposure. The leukocyte count in BALF was significantly higher in the animals exposed to BAC aerosol compared to the controls. In the lungs of rats exposed to BAC the following effects were observed: minimal perivascular, interstitial edema, focal aggregates of alveolar macrophages, interstitial mononuclear cell infiltrations, thickened alveolar septa and marginal lipoproteinosis. Conclusion: Inhalation of BAC induced a strong inflammatory response and a damage to the blood-air barrier. Reduced concentrations of CC16, which is an immunosuppressive and anti-inflammatory protein, in combination with increased IgE concentrations in BALF may be indicative of the immuno-inflammatory response in the animals exposed to BAC aerosol by inhalation. Histopathological examinations of tissue samples from the BAC-exposed rats revealed a number of pathological changes found only in the lungs

Potent Inhibition of Both Human Interferon-gamma Production and Biologic Activity By the Clara Cell Protein Cc16

The Clara cell 16 kD protein (CC16), the predominant product of the Clara cells lining the bronchiolar epithelium, is thought to protect the respiratory and urogenital tract from unwanted inflammatory reactions through its immunosuppressive action. In this report, we show evidence that CC16 establishes an anti-inflammatory activity by interfering with the interferon-gamma (IFN-gamma)-mediated actions of the cytokine network. The HuIFN-gamma production of stimulated single-donor peripheral blood mononuclear cells is inhibited by the presence of doses of CC16 in the range of 10(-12) M, with a maximal inhibition (up to 95%) when interleukin-2 is used as a stimulating agent. CC16 also diminishes the biologic activity of IFN-gamma: both the antiviral activity and the stimulation of phagocytosis by IFN-gamma, measured by means of chemiluminescence, are reduced in the presence of CC16. These observations indicate that CC16 acts as an anticytokine and could give new insight in the potential role of the Clara cells