Children's National Health System Posters

Title

IPSE, a parasite derived host immunomodulatory protein, is a promising therapeutic for pediatric bladder pain

Poster Number

349

Document Type

Poster

Status

Fellow

Abstract Category

Basic Biomedical Sciences

Keywords

Genitourinary schistosomiasis, IPSE, parasitology, bladder pain

Publication Date

Spring 2018

Abstract

Background:

Pediatric bladder pain syndromes and associated dysfunctional voiding behavior cause a significant decline in the quality of life of patients and their families. Currently available treatments have limited efficacy. Therefore, novel therapeutic options are needed. We previously reported, in a bladder pain model of ifosfamide-induced hemorrhagic cystitis (HC), that systemic administration of Schistosomiasis haematobium derived protein H-IPSEH06 (IL-4 inducing principle from Schistosoma mansoni eggs), relieves carrageenan-induced inflammatory pain. Furthermore, H-IPSEH06 is superior to mesna in alleviating HC by binding IgE on basophils and inducing IL-4 expression, promoting urothelial proliferation and translocating to the nucleus to modulate gene expression.

Objective:

We speculate that local bladder injection of IPSE ortholog IPSEH03 (H-IPSEH03) might have a more potent effect in treating HC with less potential side effects compared with systemic administration of IPSEH06.

Methods/Design:

C57BL/6 female mice underwent bladder wall injection of H-IPSEH03, or H-IPSE mutant lacking the nuclear localization sequence (H-IPSEHO3NLS) followed by exposure to ifosfamide. Urinary frequency was assessed by urine spot assays. Elicited pain scores were recorded in a blinded fashion. Mouse bladders were harvested, and evaluated for microscopic and macroscopic edema and hemorrhage. Bladder tissue was subjected to histologic analysis.

Results/Discussion:

HC mice that underwent bladder injection of H-IPSEH03 had decreased pain response compared to HC mice. Pain tolerance conferred by H-IPSEH03 was reversed by blockade of IL-4 or IPSEH03NLS. H-IPSEH03 improved voiding dysfunction in HC mice. Bladder wet weight (BWW) and Gray’s scoring was decreased in HC mice treated with H-IPSEH03 compared to controls.

H-IPSEH03 is a promising therapeutic for the treatment of bladder pain in a model of ifosfamide-induced cystitis by relieving HC-associated pain sensitivity. H-IPSEH03 decreases edema and hemorrhage in an IL-4 dependent fashion. H-IPSEH03 may be a novel candidate for a non-opioid analgesic and anti-inflammatory in disorders that cause bladder pain and inflammation.

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IPSE, a parasite derived host immunomodulatory protein, is a promising therapeutic for pediatric bladder pain

Background:

Pediatric bladder pain syndromes and associated dysfunctional voiding behavior cause a significant decline in the quality of life of patients and their families. Currently available treatments have limited efficacy. Therefore, novel therapeutic options are needed. We previously reported, in a bladder pain model of ifosfamide-induced hemorrhagic cystitis (HC), that systemic administration of Schistosomiasis haematobium derived protein H-IPSEH06 (IL-4 inducing principle from Schistosoma mansoni eggs), relieves carrageenan-induced inflammatory pain. Furthermore, H-IPSEH06 is superior to mesna in alleviating HC by binding IgE on basophils and inducing IL-4 expression, promoting urothelial proliferation and translocating to the nucleus to modulate gene expression.

Objective:

We speculate that local bladder injection of IPSE ortholog IPSEH03 (H-IPSEH03) might have a more potent effect in treating HC with less potential side effects compared with systemic administration of IPSEH06.

Methods/Design:

C57BL/6 female mice underwent bladder wall injection of H-IPSEH03, or H-IPSE mutant lacking the nuclear localization sequence (H-IPSEHO3NLS) followed by exposure to ifosfamide. Urinary frequency was assessed by urine spot assays. Elicited pain scores were recorded in a blinded fashion. Mouse bladders were harvested, and evaluated for microscopic and macroscopic edema and hemorrhage. Bladder tissue was subjected to histologic analysis.

Results/Discussion:

HC mice that underwent bladder injection of H-IPSEH03 had decreased pain response compared to HC mice. Pain tolerance conferred by H-IPSEH03 was reversed by blockade of IL-4 or IPSEH03NLS. H-IPSEH03 improved voiding dysfunction in HC mice. Bladder wet weight (BWW) and Gray’s scoring was decreased in HC mice treated with H-IPSEH03 compared to controls.

H-IPSEH03 is a promising therapeutic for the treatment of bladder pain in a model of ifosfamide-induced cystitis by relieving HC-associated pain sensitivity. H-IPSEH03 decreases edema and hemorrhage in an IL-4 dependent fashion. H-IPSEH03 may be a novel candidate for a non-opioid analgesic and anti-inflammatory in disorders that cause bladder pain and inflammation.