Systemic Interleukin-۶ Response after Intravesical Instillation of Bacillus Calmette-Guérin and Mitomycin C in Superficial Bladder Cancer

Interleukin-۶ (IL-۶) is proposed to play a significant role in pathogenesis of urinary bladder cancer (UBC). This role may be influenced by chemotherapy (mitomycin C; MMC) or immunotherapy (Bacillus Calmette-Guérin; BCG). A case-control study was conducted to determine IL-۶ levels in serum of newly diagnosed cases (NDC) of superficial UBC, as well as in patients treated with MMC or BCG intravesical instillation. A total sample of ۱۱۱ patients (۳۶ NDC, ۴۵ MMC and ۳۰ BCG) was included, as well as a control group of ۱۰۷ healthy controls (HC). IL-۶ was detected by enzyme-linked immunosorbent assay. Results revealed that median levels of IL-۶ were significantly elevated in NDC group (۱۵.۸ pg/mL; P<۰.۰۰۱) compared to MMC and BCG groups (۷.۵ and ۵.۳ pg/mL, respectively) or HC (۴.۴ pg/mL); while, there were no significant differences between the latter three groups (MMC, BCG and HC). Receiver operating characteristic curve analysis revealed that IL-۶ is a very good predictor of UBC in NDC group versus HC (area under the curve=۰.۸۸۵; ۹۵% confidence interval=۰.۸۲۸-۰.۹۴۲; P<۰.۰۰۱; cut-off value=۱۰.۵ pg/mL; Youden index=۰.۶۲; sensitivity=۸۰.۶%; specificity=۸۱.۳%). Logistic regression analysis confirmed this significance and IL-۶ was associated with a higher risk of UBC (odds ratio=۱.۱۸; ۹۵% confidence interval=۱.۱۱-۱.۲۶; P<۰.۰۰۱). In conclusion, this study indicated that IL-۶ level was upregulated in serum of NDC of UBC. Further, IL-۶ level was restored to normal levels after intravesical instillation of MMC or BCG.

Keywords:

Urinary bladder cancer , Interleukin-۶ , Mitomycin C , Bacillus Calmette-Guérin