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.