Interleukin-12 relieves the inhibitory effects of chemotherapeutics on the cellular immune responses of human cells
XIE Shuhua
SHEN Juan
ZHANG Yannan
YU Sifei
YANG Binyan
TAO Liang
WU Changyou
Abstract：To investigate the recovery effect and mechanism of IL-12 on the immune suppression induced by chemotherapeutic medicine, human PBMCs were stimulated with or without anti-CD3 plus anti-CD28 in the presence or absent of chemotherapeutics and IL-12. The production of m RNA and expression of IFN-γ and TNF-α were measured by different methods; the expression of IFN-γ and transcription factors including T-bet, p-STAT-1 and p-STAT-4 were analyzed by fluorescence activated cell sorter (FACS) or Western blotting. PBMCs from PPD+ individuals were stimulated with BCG for the production of cytokines in the presence or absence of chemotherapeutics and IL-12. We found that chemotherapeutics had significant suppressive effects on the production of IFN-γ and TNF-α in a dose-dependent manner, and IL-12, in a dose-dependent manner, relieved the inhibitory effect of chemotherapeutics on the cytokine production. In addition, chemotherapeutics also inhibited BCG-induced antigen-specific production of cytokines, which could be recovered by IL-12. Further study revealed that chemotherapeutics down-regulated the phosphorylation of STAT4 and STAT1 and the expression of T-bet. However, IL-12 could only recover the phosphorylation of STAT4. All the results indicated that IL-12 might play an important role in the reconstruction of immune function against the infections and cell mutations in cancer patients with chemotherapy.
Keywords：ChemotherapeuticsImmunosuppressionIL-12Immune recovery
Publication Date：2018-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：9( 461-468,475 )