ABSTRACT
Background: The innate immune response to tuberculosis infection may involve the increased production of nitric oxide and cathelicidin due to the up-regulated expression of the vitamin D receptor (VDR), though this proposed mechanism remains controversial. The aim of this study was to determine how the exposure of human monocytes to Mycobacterium tuberculosis (M. tuberculosis) DNA affects the production of nitric oxide and cathelicidin, as well as the expression of VDR. Methods: This study was performed using monocytes obtained from healthy donors. After 24 h incubation, monocytes were stimulated with M. tuberculosis DNA for 18 h to determine the expression of VDR mRNA and the production of nitric oxide and cathelicidin versus non-stimulated cells (the control group). Results: The expression of VDR mRNA was higher in the monocytes exposed to M. tuberculosis DNA compared to the control group (P = 0.020). Monocytes exposed to M. tuberculosis DNA also showed significantly increased production of nitric oxide and cathelicidin compared to the control group (P = 0.0001; P = 0.028). Conclusion: The stimulation of human monocytes with M. tuberculosis DNA increases the expression of the VDR mRNA and the production of nitric oxide and cathelicidin.
ABSTRACT
BACKGROUND: Since the advent of AIDS, tuberculosis has become a major public health problem in the western society. Therefore, it is essential that pulmonary tuberculosis be rapidly diagnosed. Light microscopic detection of acid-fast organisms in sputum has traditionally been used for rapidly diagnosing tuberculosis. However positive smears are only observed in about one-half to three-quarters of cases. Studies using PCR for diagnosing pulmonary tuberculosis disclosed several shortcomings suggesting an inability to distinguish between active and treated or in active tuberculosis. In this study, the clinkcal significance of a PCR-bases rapid technique for detecting Mycobacterium tuberculosis DNA in peripheral blood investigated. MATERIALS AND METHODS: From July 1, 1998 through to August 30, 1999, 59 patients with presumed tuberculosis, who had no previous history of anti-tuberculosis medication use whithin one year prior to this study were recruite and followed up for more than 3 months. AFB stain and culture in the sputum and/or pleural fluids and biopsies when needed were performed. Blood samples from each of the 59 patients were obtained in order to identify Mycobacterium Tuberculosis DNA by a PCR test. RESULTS: 1) Forty five out of 59 patients had a final diagnosis of tugerculosis; Twenty eight were confirmed as having active pulmonary tuberculosis by culture or biopsy. Four were clinkcally diagnosed with pulmonary tuberculosis. The othe 13 patients were diagnosed as having tuberculous pleurisy (9) and extrapulmonary tuberculosis (4). 2) Fourteen patients showed a positive blood PCR test. The PCR assay correctly identified active tuberculosis in 13 out of 14 patients. The overall sensitivity and specificity of this blood PCR assay for diagnosing tuberculosis were 29% and 93%, respectively. The positive predictive value was 93%, the negative predictive value was 29% and diagnostic accuracy was 44%. 3) Six out of 14(43%) patients with blood PCR positive tuberculosis were immunologically compromised hosts. 4) A simple chest radiograph in blood PCR positive tuberculosis patients showed variable and inconsistent findings. CONCLUSION: A peripheral blood PCR assay for Mycobacterium tuberculosis is not recommended as screening method for diagnosing active tuberculosis. However, it was suggested that the blood PCR assay could contribute to an early diagnostic rate due to its high positive predictive value.