title: Effect of herpes simplex virus vector-mediated interleukin-4 gene therapy on bladder overactivity and nociception.
abstract: We investigated the effects of replication-defective herpes simplex virus (HSV) vector expression of interleukin-4 (IL-4) on bladder overactivity and nociception. HSV vector expressing murine interleukin-4 (S4IL4) or the control vector expressing β-galactosidase (SHZ) were injected to the rat bladder wall. At 1 week after viral injection, in cystometry performed under urethane anesthesia, the S4IL4-treated group did not show the intercontraction intervals reduction during intravesical administration of 10 nM resiniferatoxin (RTx). At 2 weeks after viral injection, behavioral studies were performed on vector-injected animals in an awakened state. Freezing behavior induced by 3 μM RTx, administered for 1 min into the bladder, was significantly suppressed in the S4IL4 group compared with the SHZ group. Murine IL-4 levels examined by ELISA were significantly increased in bladder and bladder afferent dorsal root ganglia at 2 weeks after viral injection. The expression of IL-1β and IL-2 and bladder inflammatory responses were significantly suppressed in the RTx-irritated bladder of S4IL4-injected rats. These results indicate that HSV vector-mediated interleukin-4 expression in the bladder and bladder afferent pathways reduces the inflammatory response, bladder overactivity and nociceptive behavior induced by bladder irritation in the rat model. Therefore, IL-4 gene therapy could be a new strategy for treating urinary frequency and/or bladder pain.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: T
authors.initials: T
authors.lastname: Oguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Funahashi
authors.forename: H
authors.initials: H
authors.lastname: Yokoyama
authors.forename: O
authors.initials: O
authors.lastname: Nishizawa
authors.forename: W F
authors.initials: WF
authors.lastname: Goins
authors.forename: J R
authors.initials: JR
authors.lastname: Goss
authors.forename: J C
authors.initials: JC
authors.lastname: Glorioso
authors.forename: N
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D004224:Diterpenes / Q000494:pharmacology; D005260:Female; D046352:Freezing Reaction, Cataleptic; D005727:Ganglia, Spinal / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D007249:Inflammation / Q000628:therapy; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D059225:Nociception; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus / Q000235:genetics*; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D053201:Urinary Bladder, Overactive / Q000503:physiopathology / Q000628:therapy*
chemical_list: D004224:Diterpenes; D015847:Interleukin-4; C024353:resiniferatoxin