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Free Content Upregulation of inducible nitric oxide synthase and cytokine secretion in peripheral blood monocytes from pulmonary tuberculosis patients

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SETTING: Peripheral blood monocytes (PBM) are the main source of alveolar macrophages, which have an upregulation of inducible nitric oxide synthase (iNOS) in pulmonary tuberculosis (TB). TNF-α and IL-1β are thought to be involved in the immune response to mycobacterial infection.

OBJECTIVE: To identify whether iNOS expression and cytokine release of PBM are upregulated and have a connection in TB infection.

DESIGN: The expression of iNOS immunoreactivity on PBM from TB patients and normal subjects was measured by loading with anti-macrophage iNOS polycolonal primary antibody analyzed by flow cytometry. Expression of iNOS mRNA in PBM was detected by RT-PCR. The spontaneous generation of nitrite and cytokines (IL-1β and TNF-α) by cultured monocytes was also determined.

RESULTS: Compared to normal subjects, iNOS immunoreactivity, the capacity for spontaneous nitrite generation and the level of TNF-α or IL-1β secretion of PBM were significantly higher in TB patients. The amount of nitrite, TNF-α and IL-1β released from PBM of TB patients was inhibited by NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NOS. The level of iNOS immunoreactivity on PBM was highly correlated with nitrite generation both in all the subjects studied and in TB patients alone. Spontaneous TNF-α production showed a stronger correlation with nitrite production than with IL-1β.

CONCLUSION: The NO and cytokine synthase activities of monocytes appear to be concomitantly upregulated in response to mycobacterial infection. The enhanced NO generation by monocytes in TB patients may play an autoregulatory role in amplifying the synthesis of pro-inflammatory cytokines.
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Keywords: IL-1; TNF-; monocytes; nitric oxide; tuberculosis

Document Type: Regular Paper

Affiliations: Department of Thoracic Medicine II, Chang Gung Memorial Hospital, Taipei, Taiwan

Publication date: 2001-03-01

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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