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

Food Chem Toxicol. 2014 Jun:68:196-203. doi: 10.1016/j.fct.2014.03.015. Epub 2014 Mar 20.

Abstract

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.

Keywords: Immunotoxicity; Interstitial cystitis; Orphan drug; Sodium pentosan polysulfate.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Body Weight / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Immunity, Innate / drug effects
  • Immunoglobulin M / metabolism
  • Immunomodulation / drug effects*
  • Killer Cells, Natural / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred Strains
  • Organ Size / drug effects
  • Pentosan Sulfuric Polyester / pharmacology*
  • Phagocytosis / drug effects
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / metabolism
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism

Substances

  • Antineoplastic Agents
  • Immunoglobulin M
  • Pentosan Sulfuric Polyester