The regulatory effects of interleukin-12 on interleukin-18 and interferon-γ production in Egyptian breast cancer patients

Abstract

BackgroundBreast cancer is the commonest form of cancer in women throughout the world. The outcome of malignant neoplasia in human is often accompanied by defective cellular immunity. ObjectiveTo investigate the regulatory effects of IL-12 on IL-18 and IFN-γ production in patients with breast cancer. In addition, the correlations between IL-18 and IFN-γ levels with different prognostic factors. MethodsThis study included 40 female patients with histologically proved breast cancer. They were divided into two groups metastatic and non-metastatic. Peripheral blood mononuclear cells were isolated from freshly drawn heparinized blood of each subject and cultured with and without recombinant IL-12 supplementation. IL-18 and IFN-γ levels assessed using ELISA before and after the addition of IL-12. ResultsThe level of IL-18 in culture supernatants ranged from 0.69 to 0.95ng/ml with mean value of 0.8ng/ml in non-metastatic patients, whereas IL-18 in metastatic patients levels varied from 0.5 to 0.7ng/ml with a mean value of 0.6ng/ml after supplementation with IL-12. In non-metastatic patients the levels of IFN-γ ranged from 1.2 to 1.9ng/ml with mean value 1.4ng/ml while in metastatic patients the levels ranged from 0.7 to 1.2ng/ml. Statistical analysis of data revealed that the supplementation of culture with IL-12 significantly increased the mean values of IL-18 IFN-γ in different clinicopathological parameters.Univariate analysis by age, tumor size, grade, number of lymph nodes, ER-PR, IL-18 level, and HER2 neu. Indicated that patients with IL-18 level higher than the median at the diagnosis had higher survival results than those with lower IL-18 concentration. In multivariate analysis IL-18 did not have an independent influence on the survival. ConclusionFindings provide insights that interleukin-12 may be a potent stimulant of the immune response by enhancing the production of IL-18 and IFN-γ. We can suggest that, IL-12 could be used as a therapeutic agent for improving prognosis associated with breast cancer.