Effect of Bisphenol A on Murine Immune Function: Modulation of Interferon- , IgG2a, and Disease Symptoms in NZB  NZW F1 Mice Catherine Sawai, Katherine Anderson, and Debby Walser-Kuntz
Department of Biology, Carleton College, Northfield, Minnesota, USA Abstract
To investigate the effects of the estrogen receptor-binding molecule bisphenol A (BPA) on murine immune function in vivo, we fed a low dose of 2.5 µg BPA/kg body weight/day to both normal C57BL/6 and lupus-prone NZB NZW F1 (NZB/NZW) 5-week-old mice for 1 week. Analysis of concanavalin A (ConA) -stimulated splenic mononuclear cells by ELISA demonstrated that BPA-fed C57BL/6 males produced, on average, 40% less interferon- (IFN- ; p < 0.01) and C57BL/6 females 28% less IFN- (p < 0.05) compared with controls. Treated female NZB/NZW mice were monitored for lupus disease symptoms, defined as proteinuria (> 100 mg/dL albumin in urine for 2 consecutive weeks) . Before the development of proteinuria, BPA-fed NZB/NZW mice produced significantly less ConA-stimulated IFN- than did controls and displayed an average reduction of 50% in immunoglobulin G2a (IgG2a) antibody production from lipopolysaccharide (LPS) -stimulated splenocytes (p < 0.05) . It is striking that 5-week-old female NZB/NZW mice fed a 7-day low-dose course of BPA developed proteinuria an average of 7 weeks later than did controls. Once proteinuria developed, splenocytes were stimulated with ConA for cytokine analysis. The BPA-fed mice showed a dramatic reduction of 64% in IFN- production and a 32% reduction in ConA-stimulated interleukin-10 (p < 0.05) . The long-lasting effects of BPA on IFN- and IgG2a production likely contributed to the increased symptom-free period of the NZB/NZW mice. Key words: bisphenol A, C57BL/6, estrogen receptor, IgG2a, interferon-, lupus, NZB NZW. Environ Health Perspect 111:1883-1887 (2003) . doi:10.1289/ehp.6359 available via http://dx.doi.org/ [Online 29 August 2003]
Address correspondence to D. Walser-Kuntz, Department of Biology, Carleton College, One North College St., Northfield, Minnesota 55057 USA. Telephone: (507) 646-5756. Fax: (507) 646-5757. E-mail: dwalser@carleton.edu We thank M. Muehlegger, M. Finnerty, M. Chaurushiya, A. Park, and N. Scott for their help with these experiments. This work was supported by National Institutes of Health grant R15 AI50595-01 and a Faculty Development Endowment grant from Carleton College. The authors declare they have no competing financial interests. Received 31 March 2003 ; accepted 28 August 2003.
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