Reduced Cytokine Secretions by LAK Cells of Pulmonary Tuberculosis Patients in Response to Tumor Targets In Vitro

Activation of macrophages and other immune components to release a series of proinflammatory cytokines is one of the first events in innate resistance to intracellular infections. Severe manifestations of tuberculosis (TB) could be caused by alterations in the balance of these cytokines. In this study, lymphokine-activated killer (LAK) cells of TB patients and normal individuals were generated by stimulation with cytokines in vitro. The LAK cells of both groups were further triggered with allogeneic tumor targets. Cytokines interferon-g (IFN-g), tumor necrosis factor-a (TNF-a), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were estimated in the supernatants generated in the two groups. The aim was to see if infection with TB influenced the secretory capacity of the immune cells in vitro. Reduced cytokine profiles were observed in TB patients, indicating defective interactions between patient effector cells with allogeneic transformed cells compared with normal individuals. Partial restoration of IFN-g production was seen with a combination of cytokines interleukin-2 (IL-2) and IL-12 in TB patients. Based on the in vitro observations, we hypothesize that in vivo also there is diminished immune cell activation of effector cells in response to the presence of infected macrophages. This probably leads to a diminished secretory function that can be corrected by the use of such cytokines as IL-2 and IL-12. The effector populations of TB patients are probably in a state of target-induced anergy, allowing the bacteria to thrive, and immunomodulatory cytokines that improve the host immune response toward countering mycobacterial infection