title: Immunomodulatory activity of orphan drug Elmiron® in female B6C3F1/N mice.
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.
authors.affiliation: Toxicology Branch, Division of National Toxicology Program, National Institute of Environmental Health Sciences, NIH, RTP, NC, United States. Electronic address: thakursa@niehs.nih.gov.
authors.forename: Sheetal A
authors.initials: SA
authors.lastname: Thakur
authors.affiliation: Integrated Laboratory Systems, RTP, NC, United States.
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
authors.affiliation: Virginia Commonwealth University, Richmond, VA, United States.
authors.forename: Kimber L
authors.initials: KL
authors.lastname: White
authors.affiliation: Virginia Commonwealth University, Richmond, VA, United States.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Smith
authors.affiliation: Virginia Commonwealth University, Richmond, VA, United States.
authors.forename: Wimolnut
authors.initials: W
authors.lastname: Auttachoat
authors.affiliation: Toxicology Branch, Division of National Toxicology Program, National Institute of Environmental Health Sciences, NIH, RTP, NC, United States. Electronic address: germolec@niehs.nih.gov.
authors.forename: Dori R
authors.initials: DR
authors.lastname: Germolec
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D007075:Immunoglobulin M / Q000378:metabolism; D056747:Immunomodulation / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007075:Immunoglobulin M; D010426:Pentosan Sulfuric Polyester
keywords: Immunotoxicity; Interstitial cystitis; Orphan drug; Sodium pentosan polysulfate