Cytokines and acute phase serum proteins as markers of inflammatory regression during the treatment of pulmonary tuberculosis* Citocinas e proteínas de fase aguda do soro como marcadores de regressão da resposta inflamatória ao tratamento da tuberculose pulmonar

Objective: To evaluate the pattern of pro-inflammatory cytokines, anti-inflammatory cytokines and the acute phase response (APR) as markers of the response to treatment of pulmonary tuberculosis. Methods: Twenty-eight patients with pulmonary tuberculosis were evaluated at three time points: pretreatment (T0), treatment month 3 (T3) and treatment month 6 (T6). Levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukine-10 (IL-10) and transforming growth factor-beta (TGF-β) were determined using ELISA in the supernatant of peripheral blood mononuclear cell and monocyte culture. Levels of total protein, albumin, globulins, C-reactive protein (CRP), alpha-1-acid glycoprotein (AAG) and erythrocyte sedimentation rate (ESR) were also determined. All of these parameters were also evaluated, only once, in a group of healthy controls. Results: In relation to controls, patients presented cytokine levels and APR that were higher at T0, lower at T3 and either lower (TNF-α, IL-10, TGF-β, AAG and ESR) or normal (IFN-γ and CRP) at T6. Conclusions: For individuals with negative smear sputum microscopy, CRP, AAG and ESR are potential markers of pulmonary tuberculosis and of the need for treatment; CRP (T0 > T3 > T6 = reference) can also be a marker of treatment response. In the patients, the Th0 profile (IFN-γ, IL-10, TNF-α and TGF-β), inducer of and protector against inflammation, predominated at T0, whereas the Th2 profile (IL-10, TNF-α and TGF-β), protecting against the harmful pro-inflammatory effect of the remaining TNF-α, predominated at T6. The behavior of IFN-γ (T0 > T3 > T6 = controls) suggests its use as a marker of treatment response.