Association of Reduced Tumor Necrosis Factor Alpha, Gamma Interferon, and Interleukin-1β (IL-1β) but Increased IL-10 Expression with Improved Chest Radiography in Patients with Pulmonary Tuberculosis

Abstract

ABSTRACT Mycobacterium tuberculosis infection is a major world health issue. The early identification of patients at risk for a poor response to anti- M. tuberculosis therapy would help elucidate the key players in the anti- M. tuberculosis response. The objective of the present study was to correlate the modulation of cytokine expression (interleukin-1 [IL-1], IL-6, IL-8, IL-10, IL-12, gamma interferon [IFN-γ], interferon-inducible protein [IP-10], and monocyte chemotactic protein 1 [MCP-1]) with the clinical response to 2 months of intensive therapy. From January to December 2007, 40 M. tuberculosis -infected patients and 40 healthy patients were recruited. After exclusion for diabetes, 32 patients and 36 controls were analyzed. The clinical responses of the M. tuberculosis -infected patients on the basis of the findings of chest radiography were compared to their plasma cytokine levels measured before and after 2 months of intensive anti- M. tuberculosis therapy and 6 months of therapy with human cytokine antibody arrays. Chest radiographs of 20 of 32 M. tuberculosis -infected patients showed improvement after 2 months of intensive therapy (early responders), while the M. tuberculosis infections in 12 of 32 of the patients resolved after a further 4 months (late responders). The levels of expression of TNF-α, MCP-1, IFN-γ, and IL-1β were decreased; and the level of IL-10 increased in early responders. After adjustment for age, gender, and the result of sputum culture for M. tuberculosis , significant differences in the levels of MCP-1 and IP-10 expression were observed between the early and the late responders after 2 months of intensive anti- M. tuberculosis therapy. Due to the interpatient variability in IP-10 levels, intrapatient monitoring of IP-10 levels may provide more insight into the M. tuberculosis responder status than comparison between patients. Plasma MCP-1 levels were normalized in patients who had resolved their M. tuberculosis infections. Further studies to evaluate the association of the modulation in MCP-1 levels with early and late responses are warranted.