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[Interleukin-12 restores and promotes the T-cell immune function inhibited by 5-fluorouracil].
- Source :
-
Ai zheng = Aizheng = Chinese journal of cancer [Ai Zheng] 2007 Aug; Vol. 26 (8), pp. 801-8. - Publication Year :
- 2007
-
Abstract
- Background & Objective: Currently, 5-fluorouracil (5-FU) is still one of the widely applied chemotherapeutic agents for tumors. Interleukin-12 (IL-12) can promote the differentiation of Th1 cells and induce the production of interferon-gamma (IFN-gamma) by CD8+ T cells. This study was to investigate the suppression mechanism of 5-FU on the immune response mediated by T cells from normal human peripheral blood, and to determine the effect of IL-12 on the immune suppression induced by 5-FU.<br />Methods: The effects of 5-FU on the proliferation of peripheral blood mononuclear cells (PBMCs) and liver cancer cell line HepG2 were examined. PBMCs were stimulated with either anti-CD3 alone or anti-CD3 plus anti-CD28 in the presence or absence of 5-FU at different concentrations (0.20-50.00 microg/ml). The level of IFN-gamma in the culture supernatant was determined by ELISA. PBMCs were pretreated with 5-FU and stimulated with anti-CD3 and anti-CD28 for 2 days. The proportions of CD4+IFN-gamma+, CD8+IFN-gamma+, CD4+IL-2+ and CD8+IL-2+ T cells, and the expression of CD25 on CD4+ and CD8+ T cells were examined by flow cytometry (FCM). PBMCs were cultured in different combinations with anti-CD3 plus anti-CD28, IL-12 and/or 5-FU for 48 h. IFN-gamma level in the supernatant was detected by ELISA. The expression of IFN-gamma on CD4+ and CD8+ T cells were examined by FCM.<br />Results: 5-FU inhibited the proliferation of HepG2 cells and PBMCs, and suppressed INF-gamma production in PBMCs in a dose-dependent manner. The proportions of immune T cells were lower in 5-FU-pretreated PBMCs than in control PBMCs (0.7% vs. 2.1% for CD4+IFN-gamma+ T cells, 2.2% vs. 3.9% for CD8+IFN-gamma+ T cells, 0.7% vs. 2.5% for CD4+IL-2+ T cells, 0.2% vs. 0.4% for CD8+IL-2+ T cells). Both the positive rate and mean fluorescence intensity (MFI) of CD25 on CD4+ and CD8+ T cells were decreased after pretreatment of 5-FU. When stimulated by anti-CD3 and anti-CD28, the proportions of CD4+IFN-gamma+ and CD8+IFN-gamma+ T cells were 1.1% and 3.2% before adding IL-12, and 1.6% and 4.1% after treatment of IL-12. When stimulated by anti-CD3, anti-CD28, and 5-FU, the proportions of CD4+IFN-gamma+ and CD8+IFN-gamma+ T cells were 0.5% and 1.1% before adding IL-12, and 1.0% and 2.5% after treatment of IL-12.<br />Conclusions: 5-FU could inhibit the proliferation of HepG2 cells and the immune function of PBMCs. IL-12 could restore the T-cell immune function inhibited by 5-FU.
- Subjects :
- Antibodies, Monoclonal immunology
CD28 Antigens immunology
CD3 Complex immunology
CD4-Positive T-Lymphocytes cytology
CD4-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes cytology
CD8-Positive T-Lymphocytes metabolism
Cell Line, Tumor
Cell Proliferation drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Flow Cytometry
Fluorouracil antagonists & inhibitors
Humans
Immunosuppressive Agents pharmacology
Interferon-gamma metabolism
Interleukin-2 metabolism
Interleukin-2 Receptor alpha Subunit metabolism
Leukocytes, Mononuclear cytology
Leukocytes, Mononuclear drug effects
Liver Neoplasms pathology
Lymphocyte Activation drug effects
Fluorouracil pharmacology
Interleukin-12 pharmacology
Leukocytes, Mononuclear metabolism
Liver Neoplasms metabolism
T-Lymphocytes immunology
Subjects
Details
- Language :
- Chinese
- Volume :
- 26
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Ai zheng = Aizheng = Chinese journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 17697537