cytokines as aserum immunological markers for follow ub ulmonary tuberculosis during theraby

Abstract

ABSTRACT The aim of the present study was to determine Th1 and Th2 cytokine profile in patients with tuberculosis to identify immunological markers for follow up of the disease activity, and to asses the outcome of anti-tuberculosis treatment. - I Blood samples were collectetlifrom newly diagnosed HIV negative pulmonary tuberculosis patients and from apparently healthy individuals as controls following an informed consent. Blood samples were as well collected at several intervals during the treatmentlwith anti- tuberculosis drugs. Levels of IFN-7, TNF-ct and Th2 cytokines IL-4 and IL-10 were measured pre and during treatment using commercial available enzyme-linked immune-sorbent assay (ELISA). Data were analyzed using SPSS 20. Receiver Operating Characteristic (ROC) Curve analysis has been carried out to assess their discriminati values. Analysis has been carried out fiirther by calculating other measures of diagnostic test ve power and to determine cut-off accuracy. The results showed the median serum level of IL-4 was 20 and 35 pg/ml higher in new cases (untreated patients) and in patients under treatment with oral anti-tuberculosis, respectively, compared with that of Controls (p=001). The levels of TNF-on were significantly increased in patients before and afier the treatment than those in control (p=0.00l). New cases had the highest median level (1Opg/ml) followed by those under treatment group (6pg/ml). Levels for IFN-Iy were not statistically different between patients and controls (p=0.351). Median levels of [L10 were similar in both controls and new cases groups (35pg/ml), but lower in patients under treatment group (2_0pg/ml). Despite that, the difference in levels of IL-10 was not statistically different between patients and controls (p=O.243). ‘ " Increase in levels of IL-4 during treatment showed that Th2 immune responses still present and may indicate active disease and thus IL4 cytokine may be a possible marker for the disease activity. This increase in IL4 is supported by a decrease in TNF-oi levels and dose not conflict

1 with the finding that IFN-'y had highest level in patients under treatment as the difference between those and newly diagnosed patients was not statistically different. Since the specificity of a test is the probability that a test will produce a true negative result when used in a non-infected population while sensitivity is the probability that the test will produce a true positive result when used in an infected population, IL-4 has the potential to be used as marker for TB (specificity=9l%) having the area under the curve AUC of .659. TNF-ct can be used as marker for TB, having that the (AUC) for TNF-11 is .824 (95°/pl CI: .737 - .912). For the chosen cut-off level of 5pg/ml, it has a sensitivity of 85% and a lower specificity of 70%. TNF-ct test is most beneficial where prevalence is very low or very high.