Journal article
Dose-dependent synergy of Th1-stimulating cytokines on bacille Calmette-Guérin-induced interferon-gamma production by human mononuclear cells
Clinical and experimental immunology, Vol.149(1), pp.178-185
07/2007
DOI: 10.1111/j.1365-2249.2007.03413.x
PMCID: PMC1942034
PMID: 17517055
Abstract
Successful bacille Calmette-Guérin (BCG) immunotherapy of bladder cancer depends on the proper induction of a T helper-type 1 (Th1) immune response. In this study we investigated the possible involvement of Th1-stimulating cytokines in BCG-induced interferon (IFN)-gamma production as well as their potential roles in enhancing BCG-induced IFN-gamma from human peripheral blood mononuclear cells (PBMCs). BCG efficiently induced IFN-gamma production by PBMCs in a dose-dependent manner. Neutralization of endogenous cytokines interleukin (IL)-2, IL-12 and IFN-alpha reduced BCG-induced IFN-gamma by 38%, 67% and 49%, respectively. Although single recombinant (r) IL-2, rIL-12 and rIFN-alpha induced no or a marginal amount of IFN-gamma, a combination of any two or three cytokines increased IFN-gamma production. When BCG (a subsaturated dose) was combined with mono, dual or triple cytokines, a synergy on IFN-gamma production was observed. Such a synergy was readily achievable even when minimal or low doses of cytokines were used. No saturation of IFN-gamma production was observed even when a subsaturated BCG dose was combined with very high doses of cytokines. A robust IFN-gamma production was also observed when a minimal BCG dose was combined with minimal doses of triple cytokines. In addition, we demonstrated that IL-2- and IFN-alpha-expressing rBCGs were superior to wild-type BCG for PBMC IFN-gamma induction and that combination of both rBCGs showed a synergy in IFN-gamma production. Taken together, these results suggest that combination of BCG with certain exogenous or endogenous (expressed by rBCGs) Th1-stimulating cytokines is a rational candidate for further study in bladder cancer treatment.
Details
- Title: Subtitle
- Dose-dependent synergy of Th1-stimulating cytokines on bacille Calmette-Guérin-induced interferon-gamma production by human mononuclear cells
- Creators
- X Chen - Department of Urology, University of Iowa, Iowa City, IA, USAM A O'DONNELLY Luo
- Resource Type
- Journal article
- Publication Details
- Clinical and experimental immunology, Vol.149(1), pp.178-185
- Publisher
- England
- DOI
- 10.1111/j.1365-2249.2007.03413.x
- PMID
- 17517055
- PMCID
- PMC1942034
- ISSN
- 0009-9104
- eISSN
- 1365-2249
- Grant note
- R21 CA104308-02 / NCI NIH HHS R21 CA104308 / NCI NIH HHS R01 DK066079 / NIDDK NIH HHS R01DK66079 / NIDDK NIH HHS
- Language
- English
- Date published
- 07/2007
- Academic Unit
- Urology
- Record Identifier
- 9984051521202771
Metrics
25 Record Views