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

Background: Breast 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. Objective: To investigate the regulatory effects of IL-12 on IL-18 and IFN-gamma production in patients with breast cancer. In addition, the correlations between IL-18 and IFN-gamma levels with different prognostic factors. Methods: This 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-gamma levels assessed using ELISA before and after the addition of IL-12. Results: The level of IL-18 in culture supernatants ranged from 0.69 to 0.95 ng/ml with mean value of 0.8 ng/ml in non-metastatic patients, whereas IL-18 in metastatic patients levels varied from 0.5 to 0.7 ng/ml with a mean value of 0.6 ng/ml after supplementation with IL-12. In non-metastatic patients the levels of IFN-gamma ranged from 1.2 to 1.9 ng/ml with mean value 1.4 ng/ml while in metastatic patients the levels ranged from 0.7 to 1.2 ng/ml. Statistical analysis of data revealed that the supplementation of culture with IL-12 significantly increased the mean values of IL-18 IFN-gamma 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. Conclusion: Findings provide insights that interleukin-12 may be a potent stimulant of the immune response by enhancing the production of IL-18 and IFN-gamma. We can suggest that, IL-12 could be used as a therapeutic agent for improving prognosis associated with breast cancer. (C) 2011 Alexandria University Faculty of Medicine. Production and hosting by Elsevier B.V. All rights reserved.