Role of Th1 and Th2 cytokines in BCG-induced IFN-gamma production: cytokine promotion and simulation of BCG effect

Yi Luo; Xiaohong Chen; Michael A O'Donnell

doi:10.1016/S1043-4666(02)00490-8

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Role of Th1 and Th2 cytokines in BCG-induced IFN-gamma production: cytokine promotion and simulation of BCG effect

Journal article

Peer reviewed

Role of Th1 and Th2 cytokines in BCG-induced IFN-gamma production: cytokine promotion and simulation of BCG effect

Yi Luo, Xiaohong Chen and Michael A O'Donnell

Cytokine (Philadelphia, Pa.), Vol.21(1), pp.17-26

01/07/2003

DOI: 10.1016/S1043-4666(02)00490-8

PMID: 12668155

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Abstract

Induction of a T-helper-type 1 (Th1) immune response is indispensable for successful treatment of superficial bladder cancer with BCG. In this study possible involvement of various cytokines in BCG action as well as their potential roles in enhancing and mimicking BCG effect were explored. In immunocompetent cell cultures, IFN-gamma, a major Th1 cytokine, appears to be a late responsive cytokine to BCG stimulation. Its induction requires involvement of various endogenously produced Th1 and Th2 cytokines. Functional abolishment of any one of these cytokines (IL-2, IL-6, IL-12, IL-18, GMCSF, TNF-alpha, or IFN-alpha, except IL-10) by neutralizing antibodies leads to reduced IFN-gamma production (19-82% inhibition in mouse and 44-77% inhibition in human systems, respectively). In mice cytokines IL-2, IL-12, IL-18, and GMCSF are observed to synergize with BCG for IFN-gamma production, whereas in human cytokines IL-2, IL-12, TNF-alpha, and IFN-alpha exhibit similar synergistic effects. Rational combinations of these Th1-stimulating cytokines (IL-12 plus IL-18 in mice and IL-2 plus IL-12 in humans, respectively) dramatically up-regulate IFN-gamma production that is incomparably superior to BCG for induction of this cytokine. These results suggest that combined Th1-stimulating cytokines and combinations of BCG plus selected Th1-stimulating cytokines are rational candidates for further study in the treatment of bladder cancer patients.

Adjuvants, Immunologic - therapeutic use

Animals

BCG Vaccine - therapeutic use

Cell Line, Tumor

Cells, Cultured

Culture Media, Conditioned - pharmacology

Cytokines - metabolism

Dose-Response Relationship, Drug

Enzyme-Linked Immunosorbent Assay

Female

Humans

Interferon-gamma - biosynthesis

Interleukin-2 - biosynthesis

Kinetics

Leukocytes, Mononuclear - cytology

Mice

Mice, Inbred C57BL

Spleen - cytology

Th1 Cells - metabolism

Th2 Cells - metabolism

Time Factors

Up-Regulation

Urinary Bladder Neoplasms - drug therapy

Details

Title: Subtitle: Role of Th1 and Th2 cytokines in BCG-induced IFN-gamma production: cytokine promotion and simulation of BCG effect
Creators: Yi Luo - University of Iowa
Xiaohong Chen - University of Iowa
Michael A O'Donnell
Resource Type: Journal article
Publication Details: Cytokine (Philadelphia, Pa.), Vol.21(1), pp.17-26
DOI: 10.1016/S1043-4666(02)00490-8
PMID: 12668155
ISSN: 1043-4666
eISSN: 1096-0023
Grant note: R29 CA64230 / NCI NIH HHS
Language: English
Date published: 01/07/2003
Academic Unit: Urology
Record Identifier: 9984320073302771

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