Immunomodulatory activity of orphan drug Elmiron® in female B6C3F1/N mice
Thakur SA, Nyska A, White KL Jr, Smith MJ, Auttachoat W, Germolec DR.
Food Chem Toxicol. (2014) DOI: https://doi.org/10.1016/j.fct.2014.03.015 PMID: 24657363
Interstitial cystitis (IC) is a chronic disorder characterized by bladder discomfort and urinary urgency in the absence of identifiable infection. Despite the expanding use in IC treatment and other chronic conditions, the effects of Elmiron® treatment on immune system remain unknown. Therefore, female B6C3F1/N mice were orally administered Elmiron® daily for 28-days at doses of 63, 125, 250, 500 or 1000mg/kg to evaluate its immunomodulatory effects. Mice treated with Elmiron® had a significant increase in absolute numbers of splenic macrophages (63, 500 and 1000mg/kg) and natural killer (NK) cells (250 and 1000mg/kg). Elmiron® treatment did not affect the humoral immune response or T cell proliferative response. However, innate immune responses such as phagocytosis by liver macrophages (1000mg/kg) and NK cell activity were enhanced (500 and 1000mg/kg). Further analysis using a disease resistance model showed that Elmiron®-treated mice demonstrated significantly increased anti-tumor activity against B16F10 melanoma cells at the 500 and 1000mg/kg doses. Collectively, we conclude that Elmiron® administration stimulates the immune system, increasing numbers of specific cell populations and enhancing macrophage phagocytosis and NK cell activity in female B6C3F1/N mice. This augmentation may have largely contributed to the reduced number of B16F10 melanoma tumors.