title: Interleukin-6 levels in female rats with protamine sulfate-induced chronic cystitis treated with hyaluronic acid.
abstract: OBJECTIVE
  To measure interleukin-6 levels in a protamine sulfate-induced chronic cystitis rat model treated with hyaluronic acid, and to study the correlation among interleukin-6, bladder inflammatory degree and voiding frequency.
  
  
  METHODS
  A chronic cystitis model was created in female rats by using long-term intermittent intravesical protamine sulfate (0.5 mL, 30 mg/mL). Then, hyaluronic acid (0.5 mL, 0.8 mg/mL) was also instilled intravesically in the rats. Interleukin-6 levels were analyzed with immunohistochemistry, real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was carried out to examine bladder inflammatory degree based on a four-point scoring system (from 0 - none to 3 - severe). Voiding patterns were investigated by cystometrography.
  
  
  RESULTS
  According to cystometrography, protamine sulfate-induced rats had significantly shorter intercontraction intervals and less bladder capacity (P < 0.001). The bladder tissue of the rats showed severe chronic inflammation. Immunohistochemistry, reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay showed significantly higher expression of interleukin-6 (P < 0.001). After intravesical administration of hyaluronic acid, both intercontraction intervals and bladder capacity increased significantly (P < 0.001), whereas both bladder inflammatory degree and interleukin-6 levels decreased significantly (P < 0.001). Furthermore, there was a strong correlation between interleukin-6 levels and inflammatory degree (r = 0.727, P < 0.001), and also between interleukin-6 levels and voiding frequency (r = -0.761, P < 0.001).
  
  
  CONCLUSIONS
  Intravesical administration of hyaluronic acid decreases interleukin-6 levels, as well as the severity of bladder inflammation and voiding frequency in a rat model of chronic cystitis. Interleukin-6 levels closely correlate with the inflammatory degree and voiding frequency. Thus, they can be regarded as an assessment measure of therapeutic impact.
authors: Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Department of Urology, First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
authors: Yi-Song
authors: YS
authors: Lv
authors: You-Sheng
authors: YS
authors: Yao
authors: Ming-En
authors: ME
authors: Lin
authors: Lu
authors: L
authors: Rong
authors: Bi-Hua
authors: BH
authors: Deng
authors: Jian
authors: J
authors: Huang
authors: Wei-Ping
authors: WP
authors: Hao
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000283:Administration, Intravesical; D000818:Animals; D018856:Cystitis, Interstitial / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D004195:Disease Models, Animal; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006494:Heparin Antagonists / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000494:pharmacology*; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D011479:Protamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D001743:Urinary Bladder / Q000187:drug effects / Q000276:immunology; D014554:Urination
chemical_list: D000276:Adjuvants, Immunologic; D006494:Heparin Antagonists; D015850:Interleukin-6; D011479:Protamines; D006820:Hyaluronic Acid
keywords: bladder pain syndrome; hyaluronic acid; interleukin-6; interstitial cystitis; protamine sulfate