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 treatment of IC 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 1000 mg/kg to evaluate its immunomodulatory effects. Mice treated with Elmiron® had a significant increase in absolute numbers of splenic macrophages (63, 500 and 1000 mg/kg) and natural killer (NK) cells (250 and 1000 mg/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 (1000 mg/kg) and NK cell activity were enhanced (500 and 1000 mg/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 1000 mg/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.

From bladder to systemic syndrome: concept and treatment evolution of interstitial cystitis

“… 61 Regarding the mechanism of action of oral PPS, in female B6C3F1/N mice, its administration stimulated the immune system, increasing the numbers of specific cell populations and enhancing macrophage phagocytosis and natural killer (NK) cell activity. 62 Recently, however, results from a randomized, double-blind, placebo-controlled study of patients with symptoms consistent with IC did not demonstrate a treatment effect with PPS when compared with placebo at the currently established dose. 63 …”

Clinical Remission Using Personalized Low-Dose Intravenous Infusions of N-acetylcysteine with Minimal Toxicities for Interstitial Cystitis/Bladder Pain Syndrome

“…Although pharmacological therapies have shown some benefit in control of IC/BPS symptoms, they may have a negative impact on the patient due to the inherent potential of adverse events [ 9 ]. In vivo studies using mouse models have shown that pentosan polysulfate may cause uncontrolled activation of immune function, which may lead to chronic inflammation, hypersensitivity, or autoimmunity [ 10 ]. As IC/BPS therapies continue to evolve, triple-targeted therapy using gabapentin, amitriptyline, and a nonsteroidal anti-inflammatory drug (NSAID) have demonstrated improved clinical outcomes [ 11 , 12 ].…”