Immunomodulatory activity of orphan drug Elmiron® in female B6C3F1/N mice

• Published in: Food and chemical toxicology 2014-06, Vol.68, p.196-203
• Main Authors: Thakur, Sheetal A., Nyska, Abraham, White, Kimber L., Smith, Matthew J., Auttachoat, Wimolnut, Germolec, Dori R.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Bacterial diseases; Bacterial diseases of the urinary system; Biological and medical sciences; Body Weight - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Female; Food toxicology; Human bacterial diseases; Immunity, Innate - drug effects; Immunoglobulin M - metabolism; Immunomodulation - drug effects; Immunotoxicity; Infectious diseases; Interstitial cystitis; Killer Cells, Natural - drug effects; Liver - drug effects; Liver - metabolism; Macrophages - drug effects; Macrophages - metabolism; Medical sciences; Mice; Mice, Inbred Strains; Nephrology. Urinary tract diseases; Organ Size - drug effects; Orphan drug; Pentosan Sulfuric Polyester - pharmacology; Phagocytosis - drug effects; Sodium pentosan polysulfate; Spleen - cytology; Spleen - drug effects; Spleen - metabolism; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism; Toxicology; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2014.03.015

•Elmiron administration increases the numbers of splenic macrophages and NK cells in female mice.•Elmiron administration increased the macrophage phagocytosis and NK cell activity in female mice.•Elmiron administration at 500mg/kg or 1000mg/kg caused decreases in growth of B16F10 melanoma tumors in female mice. 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.