Soluble IL-2R, IFN-γ and neopterin as immunologic markers in patients with tuberculosis

Abstract

Background: The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under-the influence of IFN-γ with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-γ and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. Method: The serum sIL-2R, IFN-γ and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-γ and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. Results: 1) The serum sIL-2R and IFN-γ levels were elevated in patients with tuberculosis when compared to those of healthy subjects (p≥0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis (2967±2132.8 pg/ml) than in healthy controls (4949±1242.1 pg/ml)(p≤0.05). 2) In the pulmonary tuberculosis group, the serum sIL-2R and IFN-γ levels were higher in patients with severe disease than those in patients with mild and moderate disease. However, the neopterin levels declined as the pulmonary tuberculosis became more severe (p≤0.01). 3) The mean serum sIL-2R and IFN-γ levels declined from 1071±1139.4 U/ml to 1023±1920.9 U/ml(p≥0.05), 41±52.8 pg/ml to 22±23.9 pg/ml(p≤0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from 3158±2272.6 pg/ml to 3737±2307.5 pg/ml(p≥0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. Conclusion: On the basis of this study, sIL-2R, IFN-γ and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.