Cytokine secretion in vivo and ex vivo following chemotherapy of Mycobacterium tuberculosis infection

Abstract

The human immune response to tuberculosis is partly mediated by the proinflammatory cytokines tumour necrosis factor (TNF), interleukin (IL)-6, and IL-8. We investigated plasma concentrations of these cytokines before and after maximal lipopolysaccharide stimulation ex vivo of whole blood leucocytes from Zambian patients. 32 patients with non-fatal tuberculosis, 25 of whom were seropositive for human immunodeficiency virus (HIV), were followed for 9 months. Patients were assessed at presentation to hospital (visit A), after 2 months' antimycobacterial therapy (visit B), and when chemotherapy was completed (visit C). Between visits A and B, patients regained weight ( P = 0·03) and became less anaemic ( P = 0·0001). At visit B, haemoglobin concentration remained lower in HIV seropositive patients ( P = 0·001) and the erythrocyte sedimentation rate (ESR), initially elevated in all patients, was higher in HIV seropositive patients (100 ± 6 mm vs. 43 ± 11 mm in 1 h in seronegative patients; P = 0·002). Plasma IL-8 concentrations were increased at visit C as was IL-8 secretion ex vivo ( P < 0·0001 at all time points). Otherwise plasma cytokine levels and secretion ex vivo remained similar throughout the study. Concurrent HIV infection resulted in persistently decreased IL-6 secretions ex vivo although ESR remained high. In summary, after antibiotic therapy in vivo IL-8 secretion ex vivo increased, which supports other data suggesting that IL-8 has a role in immunity to tuberculosis.