Tumor Necrosis Factor-Alpha and Interleukin-10 in Whole Blood Is Associated with Disease Progression in Pulmonary Mulitdrug-Resistant Tuberculosis Patients

Abstract

Background: Cytokine production profiles may reflect the clinical pictures of patients with tuberculosis (TB). Objective: We examined the relationship between cytokine levels and clinical parameters indicating the state of disease in active pulmonary TB patients. Methods: We measured interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-10 levels in whole blood after stimulation with culture filtrate protein of Mycobacterium tuberculosis in 33 multi-drug resistant (MDR)-TB and 51 non-MDR-TB patients. Results: No significant difference was found in IFN-γ production between non-MDR-TB and MDR-TB patients, but there was a marked reduction in TNF-α production in MDR-TB patients accompanied by a moderate increase in IL-10 levels. In contrast, the presence of cavity was associated with a significant increase in IFN-γ, whereas no difference in TNF-α between the cavity and non-cavity group was observed. Those who have TB lesions in the left lung showed lower levels of IFN-γ and TNF-α and higher IL-10 levels than the patients with lesions on the right side. IFN-γ levels were significantly increased in those with moderate or advanced lesions compared with patients with mild lesions. TNF-α and IL-10 levels did not change with disease severity. The number of M. tuberculosis bacilli in sputum was closely associated with TNF-α levels. The patient group with high value (+++) of sputum culture acid-fast bacilli produced significantly reduced levels of TNF-α compared with medium (++) and low (+) values. Conclusion: These findings suggest that IFN-γ, TNF-α or IL-10 production patterns in whole blood are associated with disease progression in active pulmonary TB.

Association of Antigen-Stimulated Release of Tumor Necrosis Factor-Alpha in Whole Blood with Response to Chemotherapy in Patients with Pulmonary Multidrug-Resistant Tuberculosis

“…In this study, we build upon our previous findings that TNF-α, IFN-γ and IL-10 profiles are distinct in non-MDR-TB versus MDR-TB patients [5]. Using sputum clearance as an indicator of positive responses to chemotherapies, we report that patients on anti-Mtb chemotherapies have altered TNF-α and IFN-γ levels that correlate with favorable responses to the drugs.…”

“…Cytokine production patterns in TB patients are presumed to vary according to the disease state, and we have previously reported that TNF-α was associated with MDR-TB and mycobacterial load in sputum [5]. However, our previous study was cross-sectional, limiting our ability to evaluate these correlations as markers to potentially predict outcome.…”

“…It has already been demonstrated that some MDR-TB patients produce lower levels of TNF-α but not IFN-γ compared with non-MDR-TB patients in PBMCs [27] or in whole blood [5]. Also, antigenic stimulation of peripheral blood monocytes from MDR-TB induces different trends of TNF-α and IL-12 production compared to those from non-MDR-TB patients [27].…”

“…Blood samples were drawn into heparinized Vacutainers and processed within 2 h for the cytokine whole-blood assay [5,8]. Blood was collected at the time of admission, and 2 and 6 months after the start of treatment prescribed by NMTH staff.…”

Cytokines and Chemokines inMycobacterium tuberculosisInfection

“…Further, antigen-specific IL-10 production is found in pulmonary TB patients (341, 342) and along with TNF-α production can be used to reliably distinguish between latent TB and pulmonary TB (342). In addition, increased accumulation of T REGS expressing IL-10 correlates with increased bacterial burden and more severe TB in an Indian population (343, 344) and a high level of IL-10 at the end of treatment in pulmonary TB patients is associated with TB recurrence (345). Finally, infection with helminths in TB patients results in decreased antigen-specific IFNγ and IL-17 responses, which is dependent on IL-10, as IL-10 blockade significantly increases frequencies of IFNγ producing cells (346, 347).…”