BACKGROUND: Ineffective cell-mediated immune response in human tuberculosis is associated with a depressed Th1 cytokine response and reduced production of IFN-gamma. Most persons infected with Mycobacterium tuberculosis are healthy tuberculin reactors with protective immunity, but a minority with ineffective immunity develop extensive pulmonary tuberculosis. The cell-mediated immune response is an important aspect of host resistance to mycobacterial infection and is believed to be tightly regulated by a balance between Th1 cytokines including IFN-gamma IL-12, IL-18, regulated on activation, normal T cell expressed and secreted (RANTES) and Th2 counterparts such as IL-4, monocyte chemoattractant protein-1 (MCP-1). METHODS: Proliferation and mRNA expression of IFN-gamma RANTES and MCP-1 by RT-PCR in peripheral blood mononuclear cells (PBMCs) in response to in vitro stimulation with mycobacterial antigens were compared in pulmonary tuberculosis patients with cured and treatment failure and in tuberculin-positive and tuberculin-negative healthy subjects. RESULTS: Defective proliferative responsiveness to aqueous TSP antigen was involved with treatment failure tuberculosis patients. Aqueous TSP antigen-induced IFN-gamma and RANTES mRNA expression was decreased in treatment failure tuberculosis patients compared with healthy tuberculin reactors and cured tuberculosis patients (23.1% versus 90.0% for IFN-gamma and 46.2% versus 70.0% versus 46.2% for RANTES). The frequency of MCP-1 mRNA expression to aqueous TSP antigen in treatment failure tuberculosis patients was greater than in healthy tuberculin reactors and cured tuberculosis patients (76.9% versus 40.0%). CONCLUSION: The increasing expression of MCP-1 mRNA in response to aqueous TSP antigen might be predicted to favor Th2 responses and restricted Th1 responses in treatment failure of pulmonary tuberculosis.
Chemokine CCL2 ; Chemokine CCL5 ; Cytokines ; Humans ; Immunity, Cellular* ; Interleukin-12 ; Interleukin-18 ; Interleukin-4 ; Mycobacterium tuberculosis ; RNA, Messenger ; Treatment Failure* ; Tuberculin ; Tuberculosis ; Tuberculosis, Pulmonary*