The evaluation of intravesicale hyaluronic acid application effect at the inflammatory cells in the experimental model of interstitial cystitis

The great importance of painful bladder syndrome/interstitial cystitis is continuing in the urology. Definition, nomenclature even the epidemiology has not obtained certainly, the natural progress has been still following up. Interstitial cystitis (IC) complex is a syndrome characterized by a variety of symptoms lasting longer than 6 months-lower abdominal pain, compression and irritative symptoms. IC is a disease often seen in young and middle-aged women and revealed by exclusion of other pathologies without basing on any reason. It is thought that autoimmunity, subclinical and/or chronic infection, smoking poor diet and etc. may cause the genetic etiology of IC of which the exact cause is still unknown. Much as IC is mainly considered as a bladder problem, modern studies investigating the prevalence of comorbid diseases have revealed the fact that IC can be found along with systemic visceral problems called as "chronic pelvic pain" which have broader symptoms than bladder disease. Inflammatory bowel diseases, endometriosis, fibromyalgia, panic disorders, gynecological diseases, Crohn's disease and etc. are the diseases usually accompanied with it. Nevertheless, although the cause is still not known precisely, bladder symptoms stem from the lack of impermeability of the barrier is localized in the cell wall of transitional epithelium. Normally, the bladder urothelium has the least permeability in mammalian membranes, however in case of IC, it becomes dysfunctional due to the partial loss of the urothelium umbrella cells and as we mentioned earlier this case may occur because of the differentiation of multiple changes in the smooth muscles and the protein disorders due to barrier. Although many theories have been put forward, it has been confirmed in animal and human studies in which electron microscope is utilized that inflammation has the central role in the pathogenesis of IC. Whatever the etiology is, persisting noxious stimulus causes chronic inflammation. As a result, this vicious cycle results with injury in bladder epithelium and the glycosaminoglycan (GAG) layer. Normal bladder epithelium is covered by a glycosaminoglycan layer such as chondroitin sulfate, hyaluronic acid and mucin. As a result of IC, increased permeability in this mucinous and GAG layer and variable permeability against urinary cations such as K take place. Damage can also result in excessive production of cytokines in urothelium and mast cell activation. Variability in the K ion permeability triggers the activation. The cytokines, neurotransmitters, antiproliferative factor (AFP) and mast cells increasing in the urothelium result in hyperalgesia in the IC patients. AFP may cause increase in permeability in normal urothelial epithelium and increases the release of cytokines at the same time. An increase in number of mast cells both in the submucosal layer and the detrusor layer in observed as a result of inflammation. Hunner's ulcer is seen classically in the bladder mucosa of the patient. Mast cells have increased by 6 to 10 times in examinations performed with immunohistochemical techniques in classic cases of ulcerative IC while increase of mast cells in the non-classical ulcerative IC cases is approximately by 2 times. Although several treatments are effective in the treatment of IC the most effective one among them is the replacement of GAG with deficient GAG layer in the bladder of patients. Applying hyaluronic acid intravesically is thought to protect the bladder surface and has proved to be useful in clinical studies. In a clinical study benefit obtained from a 4-week intravesical hyaluronic acid therapy was calculated as 56% and as 71% after a 7-week treatment. Studies using acute acid damaged mouse and rat bladders have revealed that intravesical hyaluronic acid treatment reduces the IL-6 level as well as reducing the inflammation and frequency of urination. And IL-6 level is directly proportional to the severity of inflammation and frequency of urination. In our study we used rabbit polyclonal antibodies and myeloperoxidase activity to indicate inflammation and inflammatory cells. We investigated CD3 to indicate T cell Lymphocytes infiltration, CD14 to indicate the monocyte infiltration, CD19 to indicate the B cell lymphocytes infiltration, CD56 to indicate the natural killer infiltration, myeloperoxidase activity to evaluate the response of the neutrophils, IL-6 to evaluate the response of inflammation. At the and of the study, it was seen that the activity at MPO in the group which was treated with single dose intravesical hyaluronic acid was close to that in the control group. Also it was found that the levels of inflammation and inflamatuar cells (B cell Lymphocytes, T cell lymphocytes, Naturel killer, Monocytes) in the therapy group determined by usin rabbit polyclonal antibodies and were evaluated with semi-quantitative methods were close to that in the control group. The result of this study with the intravesical hyaluronic aside treatment inflammatuar cells neutrophils (myeloperoxidase activity), monocytes (CD14), Naturel killers (CD56), B cell Lymphocytes (CD19), and T cell lymphocytes (CD3) are suppressed, bladder mucosal integrity is protected, thus histopathologic improvement is detected. Key words: Interstitial cystitis, GAG, hyaluronic acid, inflammation.