Mechanism on Enhancing effect of chlorinated organic solvents as groundwater pollutants on Type I Allergy

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15590111
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental pharmacy
• Research Institution: Gifu Phamaceutical University
• Principal Investigator: NAGASE Hisamitu Gifu Pharmaceutical University, Pharmaceutical Science, Professor, 薬学部, 教授 (40141395)
• Project Period (FY): 2003 – 2004
• Keywords: Type I Allergy / Tetrachlproethylene / Trichloroethylene / IL-4 / INF-γ / PCA Reaction / RT-PCR / Th1 / Th2 Balance

Research Abstract

The prevalence rate of allergic diseases such as bronchial asthma and rhinitis is increasing in industrial areas and countries. There are some reports on epidemiological studies that may suggest a link between the incidence of allergic disease and environmental pollutants, such as diesel exhaust particles (DEPs), formaldehyde and volatile organic compounds (VOC). Chlorinated organic solvents are classified into VOC, and recently have become major environmental pollutants. Previously we observed the enhancing effects of some chlorinated organic solvents, such as tetrachloroethylene (PCE) and trichloroethylene (TCE), on histamine release from rat mast cells in vitro. In the present study, we investigated the enhancing effect of low concentration of PCE and TC dissolved in drinking water on Wistar rat. The chlorinated organic solvents enhanced passive cutaneous anaphylaxis (PCA) in a dose-dependent manner. Rat mast cell RBL-2H3 were incubated with anti-dinitrophenol (DNP) monoclonal IgE antibody, and then stimulated by DNP-BSA in the presence of PCE (0.01, 0.1 and 1 mg/L) or TCE (0.03, 0.3 and 3 mg/L). The conditioned medium and cell lysate were collected, and measured IL-4, TNF-α and MCP-1 by ELISA. Each inflammatory mediator production was increased in a dose-dependent manner. Furthermore, mRNA expression of them was evaluated by semi-quantitative RT-PCR, these mRNA expressions were found to be up-regulated by the exposure of PCE and TCE. Thus, this overexpression of inflammatory mediator from RBL-2H3 exposed to PCE and TCE is associated with inflammatory response in late phase. These results suggest that PCE and TCE, even in a low concentration, may affect the immune response via the modulation of cytokine production in mast cells, and lead to the augmentation of allergic diseases.