Bee Venom-Associated Th1/Th2 Immunoglobulin Class Switching Results in Immune Tolerance of NZB/W F1 Murine Lupus Nephritis

Abstract

Background/Aims: Bee venom (BV) therapy has been used to treat inflammatory diseases including rheumatoid arthritis in humans and in experimental animals. This study was conducted to examine the therapeutic effect of BV on established lupus nephritis in New Zealand Black/White (NZB/W) F1 female mice. Methods: Beginning at 18 weeks of age, mice were given a subcutaneous injection of either BV (3 mg/kg BW) or an equal volume of saline once a week until the end of the study. To examine the effect of BV on CD4+CD25+Foxp3+ regulatory T cells, splenocytes from NZB/W mice (23 weeks of age) were treated with BV (1 µg/ml) or PBS in the presence of anti-CD3Ε (1 µg/ml) and anti-CD28 antibodies (4 µg/ml) for 48 h. Results: BV administration delayed the development of proteinuria to a significant extent, prevented renal inflammation, reduced tubular damage, and reduced immune deposits in the glomeruli. Interestingly, CD4+CD25+ regulatory T cells were significantly increased in vitro and in vivo after BV treatment. Conclusion: Collectively, the administration of BV that has immune modulating effects represents an applicable treatment of lupus nephritis in NZB/W F1 mice.