The clearance of intracellular bacteria requires the appropriate induction of proinflammatory
cytokines and
chemokines to recruit macrophages and T cells to the site of
infection. In this study, we investigated the production of tumour
necrosis factor (
TNF)-alpha,
interleukin (IL)-8 and
interferon (IFN)-gamma by the peripheral blood mononuclear cells (PBMC) of patients with
multidrug-resistant tuberculosis (MDR-TB) in response to in vitro stimulation with the 30-kDa
antigen of Mycobacterium tuberculosis. The results were compared with those from cases of newly diagnosed TB (N-TB) and TB with treatment failure (TF-TB), and healthy
tuberculin reactors (HTR). The most significantly depressed
TNF-alpha levels were found in MDR-TB patients. IFN-gamma production was depressed significantly in all groups of TB patients compared with the HTR group.
TNF-alpha secretion in response to the 30-kDa
antigen was unchanged by coculturing with recombinant human
interferon (rhIFN)-gamma, and was increased dramatically following
IL-10 neutralization with an anti-human
IL-10 antibody. The
IL-8 levels were depressed significantly in MDR-TB patients compared with N-TB patients, but were similar to the
IL-8 levels in TF-TB patients. Furthermore, rhTNF-alpha directly increased
IL-8 secretion, and
neutralizing antibody to
TNF-alpha inhibited
IL-8 production by the PBMC of MDR-TB patients that were stimulated with the 30-kDa
antigen. Taken together, these data suggest that the PBMC of MDR-TB patients typically show
TNF-alpha depression in response to the 30-kDa
antigen, and this effect is modulated by
IL-10. In addition, we highlight the role of
TNF-alpha in
IL-8 secretion in MDR-TB patients.