Dysregulated production of interferon-gamma, interleukin-4 and interleukin-6 in early tuberculosis patients in response to antigen 85B of Mycobacterium tuberculosis

Both interferon-gamma (IFN-gamma) and interleukin (IL)-4 expression in T ce lls and IL-6 expression in cells of the monocyte/macrophage lineage were mo nitored using antigen 85B (Ag85B) protein and purified protein derivative ( PPD) antigen in the early stages of tuberculosis (TB). We showed that the l evels of cell-associated IFN-gamma and IL-4 (mRNA and intracellular cytokin e) in Ag85B-stimulated T cells were significantly depressed in TB patients compared with those in healthy tuberculin reactors. On the other hand, the capacity of peripheral blood mononuclear cells (PBMC) to produce IL-6 spont aneously ex vivo was enhanced in patients (P < 0.001), but their correspond ing capacities to respond to Ag85B were not significantly different from th ose of normal donors. After 2 months of antituberculosis therapy, the mean blastogenic responses of Ag85B-stimulated PBMC from seven TB patients were increased 6.1-fold (P = 0.011). Furthermore, the proportions of both IFN-ga mma- (P < 0.01) and IL-4- (P = 0.05) producing T cells were significantly i ncreased. However, those of IL-6-producing cells were diminished in respons e to Ag85B (P = 0.05). Our results suggest that there may be an altered reg ulation of IFN-gamma, IL-4 and IL-6 to Ag85B in the early stages of TB.