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J.Health Sci., 49(3), 195-204, 2003
Effects of Various Chemicals Including Endocrine Disruptors and Analogs on the Secretion of Th1 and Th2 Cytokines from Anti CD3-Stimulated Mouse Spleen Cells
Kazuma Yano,a Shuji Ohno,a Yonako Nakajima,a Satoshi Toyoshima,b and Shizuo Nakajin*, a
aDepartment of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan and bPharmaceuticals and Medical Devices Evaluation Center, National Institute of Health Science, 3-8-21 Toranomon, Minato-ku, Tokyo 105-8409, Japan
The in vitro effects of various chemicals, such as styrene dimers, styrene trimers, alkylphenols, phthalate esters, phytoestrogens, and organotin compounds, on the production of interferon-gamma (IFN-gamma), a type 1 helper T-cells (Th1) specific cytokine, and interleukin-4 (IL-4), a type 2 helper T-cells (Th2) specific cytokine, which are secreted from anti CD3-stimulated mouse spleen cells, were examined. These chemicals suspected of having an endocrine disruptor function and to which humans may become exposed via ingestion through food, food containers, and food packaging. It was found the organotin compounds bis(tributyltin) oxide, tributyltin chloride, and dibutyltin dichloride at concentrations which did not elicit any cytotoxicity inhibited secretion of the Th1 and Th2 specific cytokines IFN-gamma and IL-4 at concentrations (0.01-0.03, 0.07-0.1, and 0.096-0.132 mu M for IC50, respectively) that were much lower than those of the other chemicals. However, these butyltin compounds exhibited similar degrees of inhibitory effects on IFN-gamma and IL-4 secretion and did not selectively inhibit the secretion of one or the other cytokine. However, diphenyltin dichloride and phenyltin trichloride enhanced the secretion of IL-4 at the comparatively low concentrations of 0.3 mu M and 1.0 mu M, respectively, although these compounds significantly inhibited IFN-gamma secretion at the same concentrations. In addition, 4-t-pentylphenol enhanced IL-4 secretion although it inhibited IFN-gamma secretion at the comparatively high concentration of 30 mu M. It was also found that some styrene trimers, phthalate esters and flavonoids as well as the alkyl phenols octylphenols and nonylphenol among others, inhibited the secretion of both cytokines at comparatively high concentrations (< 30 mu M).
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