BCG dose reduction by decreasing the instillation frequency: effects on local Th1/Th2 cytokine responses in a mouse model.
OBJECTIVE
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 Th1 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 semiquantitative RT-PCR based method.


RESULTS
A schedule of only two BCG instillations, administered in week 1 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 immune stimulating capacity and therapeutic efficacy associated with less side effects in patients remains to be investigated.
de Boer
Elizabeth C
EC
Department of Urology, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. e.c.deboer@amc.uva.nl
Rooyakkers
Sietske J
SJ
Schamhart
Denis H J
DH
de Reijke
Theo M
TM
Kurth
Karl-Heinz
KH
D000283:Administration, Intravesical; D000818:Animals; D001500:BCG Vaccine / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000276:immunology
D001500:BCG Vaccine; D016207:Cytokines