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 (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(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. Conclusions 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.