Plasma Heme Oxygenase-1 Levels Distinguish Latent or Successfully Treated Human Tuberculosis from Active Disease

被引：59

作者：

Andrade, Bruno B. ^{[1
]}

Kumar, Nathella Pavan ^{[2
]}

Mayer-Barber, Katrin D. ^{[1
]}

Barber, Daniel L. ^{[1
]}

Sridhar, Rathinam ^{[3
]}

Rekha, Vaithilingam V. Banu ^{[4
]}

Jawahar, Mohideen S. ^{[4
]}

Nutman, Thomas B. ^{[1
]}

Sher, Alan ^{[1
]}

Babu, Subash ^{[1
,2
,5
]}

机构：

[1] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA

[2] Int Ctr Excellence Res, Natl Inst Hlth, Madras, Tamil Nadu, India

[3] Govt Stanley Med Hosp, Madras, Tamil Nadu, India

[4] Natl Inst Res TB, Madras, Tamil Nadu, India

[5] NCI, Sci Applicat Int Corp, Frederick, MD 21701 USA

来源：

PLOS ONE | 2013年 / 8卷 / 05期

基金：

美国国家卫生研究院;

关键词：

PULMONARY TUBERCULOSIS; CARBON-MONOXIDE; INFECTION; DIAGNOSIS; NEOPTERIN; PROMOTES;

D O I：

10.1371/journal.pone.0062618

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Background: 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)-gamma and IL-17 and diminished levels of tumor necrosis factor (TNF)-alpha. 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.

引用

页数：6

共 32 条

[1]

[Anonymous], WHO GLOB TUB REP 201

[2]

IFN-γ-inducible protein 10 and pentraxin 3 plasma levels are tools for monitoring inflammation and disease activity in Mycobacterium tuberculosis infection [J].