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Inhibition of Interleukin-6 Attenuates Erectile Dysfunction in a Rat Model of Nerve-Sparing Radical Prostatectomy

Authors


Shinichi Yamashita, MD, Department of Urology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi Aoba-ku, Sendai, Miyagi 980-8574, Japan. Tel: (81) 22-717-7278; Fax: (81) 22-717-7283; E-mail: yamashita@uro.med.tohoku.ac.jp

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. Yamashita S, Kato R, Kobayashi K, Hisasue S, Arai Y, and Tsukamoto T. Inhibition of interleukin-6 attenuates erectile dysfunction in a rat model of nerve-sparing radical prostatectomy. J Sex Med 2011;8:1957–1964.

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