Interleukin-6: a potential biomarker of the success of tuberculosis treatment

Abstract

Background: The present measure of the success of TB treatment is fraught with problems. A cytokine biomarker(s), a qualitative and quantitative reflection of the treatment success, is thus warranted. Because TB treatment is expected to affect macrophage and mycobacteria interactions and, consequently cytokine(s) elaboration, a biomarker(s) seems crucial to assess its success. Methods & Materials: We studied the effect of anti-TB drugs isoniazid (INH), rifampicin (RIF), streptomycin (STP) and ethambutol (EMB) on IL-1β, IL-6, IL-10, IL-12 p40 and IL-12 p70 elaboration by mouse peritoneal macrophages (PMs) infected with M. tuberculosis H37Rv for 6 h, 24 h, 4 days and 7 days, in vitro, by using a multiplex suspension cytokine array system. Results: INH, at 6 h, at 0.4 μg/ml (MIC: 0.2 μg/ml) and not at 0.1 and 0.2 μg/ml, and at 24 h and on D 4 and D 7, at all the tested concentrations, significantly (p < 0.001) suppressed IL-6 elaboration. RIF, at 6 h, lacked any effect on IL-6 elaboration at 0.4 μg/ml (MIC: 0.8 μg/ml), whereas at 0.8 and 1.6 μg/ml, and at all the tested concentrations at 24 h and on D 4 and D 7, significantly (p < 0.001) inhibited IL-6 elaboration. STP, at all the time-points, at 2.5 μg/ml (MIC: 5 μg/ml), lacked any effect on IL-6 elaboration; however, at 5 and 10 μg/ml it caused significant (p < 0.001) inhibition. Surprisingly, EMB at 4, 8 and 16 μg/ml (MIC: 8 μg/ml) suppressed IL-6 elaboration at all the time-points studied. M. tuberculosis-infected untreated controls, in contrast to the uninfected ones, irrespective of the time-points, elaborated significantly (p < 0.001) high concentrations of IL-6 (infected controls, 365 ± 30.41–777.5 ± 74.45 pg/ml; uninfected controls, 15.25 ± 1.77–21 ± 1.41 pg/ml) only. Curiously, all the other cytokines (IL-1β, IL-10, IL-12 p40 and IL-12 p70) were unaffected by the drug treatments. Conclusion: M. tuberculosis -infected PMs, in vitro, elaborated IL-6 as the only major cytokine, which was significantly inhibited by anti-TB drugs. Therefore, IL-6 can be developed as a potential biomarker or biosignature to assess the success of the treatment of TB.