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PLASMA HEME OXYGENASE-1 LEVELS DISTINGUISH LATENT OR SUCCESSFULLY TREATED HUMAN TUBERCULOSIS FROM ACTIVE DISEASE
Heme Oxigenase-1
Tuberculose Latente
Agentes antituberculosos
Humanos
Adolescente
Heme Oxygenase-1
Latent Tuberculosis
Antitubercular Agents
Humans
Adolescent
Author
Affilliation
National Institutes of Health. Laboratory of Parasitic Diseases. Bethesda, Maryland, United States of America
National Institutes of Health. International Center for Excellence in Research. Chennai, India
National Institutes of Health. Laboratory of Parasitic Diseases. Bethesda, Maryland, United States of America
National Institutes of Health. Laboratory of Parasitic Diseases. Bethesda, Maryland, United States of America
Government Stanley Medical Hospital., Chennai, India
National Institute for Research in Tuberculosis. Chennai, India
National Institute for Research in Tuberculosis. Chennai, India
National Institutes of Health. Laboratory of Parasitic Diseases. Bethesda, Maryland, United States of America
National Institutes of Health. Laboratory of Parasitic Diseases. Bethesda, Maryland, United States of America
National Institutes of Health. Laboratory of Parasitic Diseases. Bethesda, Maryland, United States of America / National Institutes of Health. International Center for Excellence in Research. Chennai, India / National Cancer Institute. Science Applications International Corporation. Frederick, Maryland, United States of America
National Institutes of Health. International Center for Excellence in Research. Chennai, India
National Institutes of Health. Laboratory of Parasitic Diseases. Bethesda, Maryland, United States of America
National Institutes of Health. Laboratory of Parasitic Diseases. Bethesda, Maryland, United States of America
Government Stanley Medical Hospital., Chennai, India
National Institute for Research in Tuberculosis. Chennai, India
National Institute for Research in Tuberculosis. Chennai, India
National Institutes of Health. Laboratory of Parasitic Diseases. Bethesda, Maryland, United States of America
National Institutes of Health. Laboratory of Parasitic Diseases. Bethesda, Maryland, United States of America
National Institutes of Health. Laboratory of Parasitic Diseases. Bethesda, Maryland, United States of America / National Institutes of Health. International Center for Excellence in Research. Chennai, India / National Cancer Institute. Science Applications International Corporation. Frederick, Maryland, United States of America
Abstract
Tuberculosis (TB) is associated with oxidative stress and the induction of host anti-oxidants to counteract this response. Heme oxygenase-1 (HO-1) is a critical promoter of cytoprotection in diverse disease models including mycobacterial infection. Nevertheless, the pattern of expression of HO-1 in human tuberculosis has not been studied. Here, we examine expression of HO-1 in M. tuberculosis-exposed and -infected individuals and test its ability to distinguish active from latent and successfully treated TB cases. In addition, we assess correlations between plasma levels of HO-1 and cytokines closely associated with the immunopathogenesis of TB. Methods: Cross-sectional and longitudinal analyses of levels of HO-1, acute phase proteins and pro-inflammatory cytokines
were performed in plasma samples from individuals with active pulmonary, extra-pulmonary or latent TB infection and
healthy controls as part of a prospective cohort study in South India.
Results: Systemic levels of HO-1 were dramatically increased in individuals with active pulmonary and extra-pulmonary
tuberculosis and particularly those with bilateral lung lesions and elevated bacillary loads in sputum. HO-1 levels effectively
discriminated active from latent tuberculosis with higher predictive values than either C-reactive protein or serum amyloid
protein. Moreover, there was a marked reduction in HO-1 levels in active TB cases following anti-tuberculous therapy but
not in those who failed treatment. Pulmonary TB patients displaying the highest concentrations of HO-1 in plasma exhibited
significantly elevated plasma levels of interleukin (IL)-10, interferon (IFN)-c and IL-17 and diminished levels of tumor necrosis
factor (TNF)-a.
Conclusion: These findings establish HO-1 levels as a potentially useful parameter for distinguishing active from latent or
treated pulmonary tuberculosis, that is superior in this respect to the measurement of other acute inflammatory proteins
Keywords in Portuguese
Tuberculose PulmonarHeme Oxigenase-1
Tuberculose Latente
Agentes antituberculosos
Humanos
Adolescente
Keywords
Tuberculosis, PulmonaryHeme Oxygenase-1
Latent Tuberculosis
Antitubercular Agents
Humans
Adolescent
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