TY - JOUR
T1 - BCG dose reduction by decreasing the instillation frequency: Effects on local Th1/Th2 cytokine responses in a mouse model
AU - de Boer, Elizabeth C.
AU - Rooyakkers, Sietske J.
AU - Schamhart, Denis H. J.
AU - de Reijke, Theo M.
AU - Kurth, Karl-Heinz
PY - 2005
Y1 - 2005
N2 - Objectives: Based on the requirement of a Th1 immune response for clinical efficacy, and incited by the arbitrary induction scheme, frequent side effects and the empirical approach in improving BCG immunotherapy for superficial bladder cancer, an alternative intravesical BCG treatment schedule for dose reduction was investigated without compromising Thl cytokine induction in the bladder in a mouse model. Methods: Mice were submitted to 6 weekly BCG instillations and treatment schedules omitting intermediate instillations during this standard scheme. Th1 (IFN-gamma, IL-2, IL-12p40), and Th2 (IL-10, IL-4) cytokine responses in individual mouse bladders were measured by a semi quantitative RT-PCR based method. Results: A schedule of only two BCG instillations, administered in week I and week 6, resulted in induction of at least the same levels of IFN-gamma, IL-2 and IL-12p40 Th1 cytokine mRNA compared to 6 weekly instillations, whereas significantly lower levels of Th2 cytokines IL-10 and IL-4 mRNA were observed. Conclusions: During the 6-week period the intermediate weekly BCG instillations 2, 3, 4, and 5 do not contribute to Th1 cytokine upregulation in the bladder, provided that the BCG dose is sufficient. Whether such a reduced BCG frequency schedule has immunestimulating capacity and therapeutic efficacy associated with less side effects in patients remains to be investigated. (c) 2005 Elsevier B.V. All rights reserved
AB - Objectives: Based on the requirement of a Th1 immune response for clinical efficacy, and incited by the arbitrary induction scheme, frequent side effects and the empirical approach in improving BCG immunotherapy for superficial bladder cancer, an alternative intravesical BCG treatment schedule for dose reduction was investigated without compromising Thl cytokine induction in the bladder in a mouse model. Methods: Mice were submitted to 6 weekly BCG instillations and treatment schedules omitting intermediate instillations during this standard scheme. Th1 (IFN-gamma, IL-2, IL-12p40), and Th2 (IL-10, IL-4) cytokine responses in individual mouse bladders were measured by a semi quantitative RT-PCR based method. Results: A schedule of only two BCG instillations, administered in week I and week 6, resulted in induction of at least the same levels of IFN-gamma, IL-2 and IL-12p40 Th1 cytokine mRNA compared to 6 weekly instillations, whereas significantly lower levels of Th2 cytokines IL-10 and IL-4 mRNA were observed. Conclusions: During the 6-week period the intermediate weekly BCG instillations 2, 3, 4, and 5 do not contribute to Th1 cytokine upregulation in the bladder, provided that the BCG dose is sufficient. Whether such a reduced BCG frequency schedule has immunestimulating capacity and therapeutic efficacy associated with less side effects in patients remains to be investigated. (c) 2005 Elsevier B.V. All rights reserved
U2 - https://doi.org/10.1016/j.eururo.2005.05.004
DO - https://doi.org/10.1016/j.eururo.2005.05.004
M3 - Article
C2 - 15963631
SN - 0302-2838
VL - 48
SP - 333
EP - 338
JO - European Urology
JF - European Urology
IS - 2
ER -