The study on the function and cell source of interleukin‐6 in interstitial cystitis/bladder painful syndrome rat model

Abstract Objective The elevated expression of interleukin‐6 (IL‐6) in patients with interstitial cystitis/bladder painful syndrome (IC/BPS) has been demonstrated, but the role of IL‐6 in IC/BPS and its source remain to be explored. Methods IC/BPS rat model was created in female rats by using long‐term intermittent intravesical hyaluronidase (0.5 ml, 4 mg/ml). After modeling, IL‐6 stimulation group, and anti‐IL‐6R group were treated with recombinant rat IL‐6 and tocilizumab, respectively. Symptomatic changes were detected by Vonfrey pain score and urodynamics, and hematoxylin‐eosin (HE) staining, mast cell staining and Masson staining were used to evaluate the changes of inflammation in the bladder tissue of rats. Cell sources of IL‐6 was explored through enzyme linked immunosorbent assay (ELISA) test, reverse transcription polymerase chain reaction (RT‐PCR), and western‐blot test on the supernatant of coculturing rat bladder epithelial cells and rat macrophages. Results The Vonfrey pain scores of the model group and IL‐6 stimulation group were significantly higher than those of the control group, while the anti‐IL‐6R group were significantly lower (p < .05). Compared with the blank control group, urodynamic results showed that the urination interval of the model group and IL‐6 stimulation group was significantly shortened, and the maximum bladder capacity was significantly reduced (p < .05), and anti‐IL‐6R treatment significantly alleviated the inflammatory response of bladder tissue. The results of HE, Mast cell staining, and Masson staining showed that the inflammatory response of bladder tissue after anti‐IL‐6R treatment was significantly reduced. Through cells coculture, the relative expression of IL‐6 from model group was found significantly higher than blank control group by RT‐PCR, ELISA, and western blot test (p < .05). Conclusions IL‐6 played an essential role in the development of IC/BPS rat model as a proinflammation cytokine. Further evidence from coculture proved that macrophages are the cell resource of IL‐6 in IC/BPS