Inhibition of interleukin-6 attenuates erectile dysfunction in a rat model of nerve-sparing radical prostatectomy

J Sex Med. 2011 Jul;8(7):1957-64. doi: 10.1111/j.1743-6109.2011.02283.x. Epub 2011 Apr 14.

Abstract

Introduction: The precise mechanisms underlying erectile dysfunction (ED) occurring after cavernous nerve (CN)-sparing surgery remain to be determined. Aim. To evaluate the expression of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) after CN injury, and the effect of inhibiting IL-6 bioactivity on nerve injury-related ED.

Methods: Male Sprague-Dawley rats were divided into three groups: sham operation; bilateral CN dissection without crushing or cutting; and bilateral CN resection. In the interventional experiment, male rats underwent bilateral CN dissection, and anti-rat IL-6 antibody in phosphate-buffered saline (PBS) or vehicle alone was injected intraperitoneally immediately and 24 hours after CN dissection.

Main outcome measures: One, 3, 7, 28, and 56 days after surgery, the expression of IL-6 and IL-6R in the major pelvic ganglion (MPG) was examined by real-time polymerase chain reaction. In the interventional experiment, erectile function was assessed by determining intracavernous pressure divided by arterial pressure (ICP/AP) during electrical pelvic nerve stimulation at 4 weeks after surgery in the anti-IL-6-injected rats and PBS-injected rats. The degree of nerve injury was also evaluated by retrograde dye tracing with Fluorogold.

Results: The expression levels of IL-6 and IL-6R were increased in the early period of CN injury, as compared with the sham group. IL-6 expression on day 1 was particularly enhanced. Four weeks after CN dissection, the anti-IL-6 group had greater ICP/AP and more FG-positive cells than the PBS group.

Conclusions: Expression levels of IL-6 in the MPG were increased in the acute phase following CN injury. Inhibition of IL-6 bioactivity attenuated ED following CN dissection. Thus, the suppression of excess inflammatory responses in the acute phase may lead to improvements in ED occurring after nerve-sparing radical prostatectomy.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Erectile Dysfunction / etiology
  • Erectile Dysfunction / immunology*
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / biosynthesis*
  • Male
  • Penile Erection / immunology*
  • Prostatectomy / adverse effects*
  • Prostatectomy / methods
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-6 / biosynthesis*

Substances

  • Interleukin-6
  • Receptors, Interleukin-6