Discussion
This study demonstrated that the IL-1 and neopterin levels of the patients with NMIBC significantly decreased after TURBT, however these decreases did not continue after intravesical BCG immunotherapy (Figure 2 and 3). Although the IL-1 levels of the patients were higher than the levels of the controls, this difference was not statistically significant. According to our best knowledge, there has been no study in literature to investigate IL-1 levels in blood samples of patients with NMIBC. Some studies have evaluated IL-1 levels in urine samples of patients with NMIBC in hours after intravesical BCG therapy (13,14). They found that the urine IL-1 levels increased after intravesical BCG therapy and reported that the result reflected the local inflammatory response to BCG. They also suggested further studies that would evaluate the possible role of IL-1 against NMIBC(14). We investigated the effect of treatment (TURBT and intravesical BCG) on the IL-1 level in the blood of the patients with NMIBC and our results showed that TURBT caused a significant decrease in the IL-1 level. This finding is novel to the literature. This reduction may be related to the decrease in tumor weight or tumor removal.
Similar to the reduction of the IL-1 level, the neopterin levels of the patients with NMIBC decreased after TURBT in our study. According to the best of our knowledge, there is only one study that investigated neopterin levels in blood samples of patients with NMIBC (15). In this study, the authors measured the neopterin levels before, at 4th, 24th, 48thand 96th hour after intravesical BCG and investigated the role in immune response of neopterin after BCG. They found that the highest blood neopterin levels were found 48 hours after intravesical BCG therapy and were significantly higher than levels before BCG, 4 hours and 24 hours after BCG. They also suggested that neopterin in serum might be used as a parameter for monitoring treatment course. We differently investigated neopterin levels after TURBT. Similar to the decrease of IL-1, the reduction of neopterin levels after TURBT may be related to the decrease in tumor weight and tumor removal.
There have been some studies that investigated IL-6 levels in patients with bladder cancer (16-20). Only one (20) of these studies evaluated this cytokine in blood samples of patients. In the other studies, it was measured either in urine samples (18,19) or tumor issues (16,17). Kumari et al (20) evaluated serum the IL-6 levels in 72 patients with bladder cancer (52 NMIBC and 20 MIBC). They divided the patients into 2 groups according to the presence of recurrence and found that the IL-6 levels of the patients with recurrent were higher than the patients with non-recurrent. They also reported the association high concentration of some cytokines such as IL-6 with poor recurrence free survival in the patients with bladder cancer. However, in their study, the IL-6 levels were not compared before and after the treatment of bladder cancer. Therefore we do not know the change of IL-6 levels after the treatment in their study. We differently investigated the IL-6 levels before and after TURBT and intravesical BCG instillation in only NMIBC. The results of our study showed that the IL-6 levels before the treatment did not statistically change after both TURBT and intravesical BCG therapy. Therefore, according to our outcomes, IL-6 is not a proper biomarker to follow patients with NMIBC.
Similar to IL-6, there have been some studies that investigated IL-8 levels in urine of patients with NMIBC (19,20). The results of these studies showed that there was a significant relationship between high IL-8 levels and poor prognosis in the follow-up of NMIBC. However, they did not investigate the IL-8 levels in the blood of the patients. We compared the IL-8 levels in the blood of the patients with NMIBC with the healthy controls and found that there was no significant difference. We also compared the preoperative IL-8 levels with the IL-8 levels after TURBT and intravesical BCG therapy. We found that the preoperative IL-8 levels did not change after treatment of NMIBC. Therefore, although the previous studies suggested that urinary IL-8 levels in patients might be used to predict the prognosis of NMIBC, the finding of our study showed that serum IL-8 level is not an available cytokine to use in patients with NMIBC.
There were some limitations in our study. The first one was that we did not follow the patients after intravesical BCG therapy. Therefore we could not assess the progression and recurrence status of the patients. The other limitations were small sample size and choice of cut-off times for blood sampling. The last limitation was that we measured the cytokines only in blood samples and did not perform urine tests.