The Role of Neopterin and Biomarkers of Inflammation in the Monitoring оf Treatment Efficacy for Pulmonary Tuberculosis

Neopterin (2-amino-4-hydroxy6-pteridine) is an indicator of cell-mediated immunity. This biomarker is synthesized by activated monocytes, macrophages and dendritic cells that are stimulated by gamma-interferon produced by T-lymphocytes. In Tuberculosis (TB) science neopterin is considered to be a diagnostic marker of this disease, as an indicator of the activation of TB from the latent form, and an indicator for monitoring the effectiveness of anti-TB therapy. Gaptoglobin (GB), ceruloplasmin (CP), and serumucoids (SM) is a complex of biomarkers of inflammation (BI), which, despite their nonspecificity, can reflect the activity of TB process as a process of chronic inflammation, and can also be used to monitor the effectiveness of anti-TB treatment. Literature review shows that the study of the dynamics of the content of neopterin in patients with different treatment effects has not been performed yet. Therefore its role in monitoring the effectiveness of anti-TB therapy remains unclear. The purpose of study was to determine the dynamic of levels of neopterin and biomarkers of inflamation in patients with positive and delayed or/and negative effects of treatment with standard anti-TB treatment regimens, to determine the role of neopterin as a monitoring indicator of treatment efficacy. Materials and methods. 80 patients with pulmonary TB were included in the study. The first group included 30 patients with positive effect to the anti-TB treatment, which had conversion of bacteria excretion after 60 doses of therapy. The second group included 50 patients with delayed or/and negative effects on treatment, that had conversion of bacteria excretion after 90-120 doses of therapy (subgroup A had 30 patients) and had a result of treatment “Failure” after 120 doses (20 patients). The control group consisted of 20 practically healthy persons. The diagnostic samples were carried out in 3 stages: the first was at the beginning of anti-TB treatment; the second was after 60 doses for the first group, after 90-120 doses for the second group; the third was for the first group and the subgroup A at the end of anti-TB treatment, for the subgroup B with determined of the result of "Failure". Results and discussion. The content of neopterin in blood serum was determined by ELISA method with using of the Awareness Technology Stat Fax 303 Plus Microstrip Reader (USA) and standard set of Neopterin-96 reagents manufactured by IBL (Germany). The content of BI was determined by spectrophotometric method on standard sets produced by “Reagent” (Ukraine). Mann-Whitney criterion was used, while significant differences were considered as such at p <0.05. Statistical data processing was performed using Statistica 6.1 software (StatSoft). Significant (p <0.05) increase of all biomarkers was determined at the 1 monitoring stage in both groups of TB patients, in comparison with the control group. Neopterin was higher to 47.5% and 53.2%, GB was to 52.5% and 48.5%, CP was to 52.5% and 45.4%, SM was to 216.9% and 285.7%, in the first and second group, respectively. At the 2 monitoring stage neopterin and BI levels were significant (p <0.05) decrease in the first group. Neopterin decreased on 25.5%, CP was on 24%, GB was on 23.2%, SM was on 36.5%. In the second group there was no such dynamics. At the 3 monitoring stage the levels of the studied indicators approached the norm and did not differ from the control, except CP. In subgroup A levels of all indicators were higher than in first group, and in sugroup B. Conclusions. Positive effect of anti-TB therapy was accompanied by decreasing of neopterin and BI levels. Delayed effect, when bacterial excretion persists and there was a negative x-ray dynamics more than after 2 months of therapy, inflammation and cell immunity parameters were stable.