Effect of bisphenol A on murine immune function: modulation of interferon-gamma, IgG2a, and disease symptoms in NZB X NZW F1 mice.
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 micro g BPA/kg body weight/day to both normal C57BL/6 and lupus-prone NZB X NZW F(1) (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-gamma (IFN-gamma; p < 0.01) and C57BL/6 females 28% less IFN-gamma (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-gamma 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-gamma production and a 32% reduction in ConA-stimulated interleukin-10 (p < 0.05). The long-lasting effects of BPA on IFN-gamma and IgG2a production likely contributed to the increased symptom-free period of the NZB/NZW mice.
Sawai
Catherine
C
Department of Biology, Carleton College, Northfield, Minnesota 55057, USA.
Anderson
Katherine
K
Walser-Kuntz
Debby
D
D000818:Animals; D001559:Benzhydryl Compounds; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis*; D008177:Lupus Vulgaris / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D010636:Phenols / Q000633:toxicity*; D013154:Spleen / Q000276:immunology*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D016207:Cytokines; D004968:Estrogens, Non-Steroidal; D007074:Immunoglobulin G; D007371:Interferon-gamma; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds