A study of the role of IL-12 in pulmonary tuberculosis using the whole blood flowcytometry technique.

Pulmonary tuberculosis remains a major health problem. It is caused by Mycobacterium tuberculosis, which elicits a T-cell dependent immune response, initiated by monocytes through a large number of cytokines of which interleukin-12 is thought to play a critical role in initiation and regulation of T-helper (Th-1) like responses. To better understand the role of IL-12 in pulmonary tuberculosis patients, intracellular IL-12 in peripheral blood-derived monocytes was examined by flowcytometery. The percentage of monocytes producing IL-12 was measured after invitro stimulation of heparinized whole blood with mycobacterial protein antigens (culture filtrate). Of the 22 active tuberculosis patients, 17 were recent cases and 5 recurrent cases. Healthy controls were 14 individuals with detectable reaction to purified protein derivative (PPD+) and 14 without detectable reaction to PPD. The role of different factors affecting disease outcome such as treatment, age, gender, smoking, severity of disease and presence of other complications on the percentage of monocytes producing IL-12 was studied. Recurrent TB patients had a higher number of monocytes producing IL-12 in unstimulated cultures compared to other groups (P < 0.001). However, after in vitro stimulation there was a significant decrease in the number of monocytes producing IL-12 in recurrent TB patients as compared to recently diagnosed TB patients and healthy PPD+ individuals (P < 0.001). Antituberculosis chemotherapy was the only factor that had significant effect on the percentage of monocytes producing IL-12 (p < 0.05) while other studied factors did not show significant effect (p > 0.05). It is concluded that IL-12 plays a prominent regulatory role in tuberculosis.

Human natural killer T cells (NKT), NK and T cells in pulmonary tuberculosis: potential indicators for disease activity and prognosis.

One third of the world's population is infected with Mycobacterium tuberculosis (MTB). However, active disease can develop only in a small percentage, when the immunity is weakened. The acquired immune response to MTB is primarily mediated by T cells. Natural killer (NK) cells play a central role in innate immunity to microbial pathogens. Human NKT cells have characteristics of both T and NK cells and also exhibit antimycobacterial activity. This work aimed to enumerate T, NK and NKT cells in active pulmonary TB compared with healthy controls and to study the correlation between these cells with different factors affecting prognosis of pulmonary TB as disease severity, complications or associated diseases, antitubrculosis chemotherapy, and age & gender. Of the 22 active tuberculosis patients examined, 17 were recent cases and 5 recurrent. Healthy controls were divided into 14 individuals with detectable reaction to purified protein derivative (PPD+) and 14 individuals without detectable reaction to PPD-. The percentages of T, NK and NKT cells in erythrocyte-lysed whole blood samples were determined using flowcytometry. The percentage of NKT cells was significantly higher among the recently diagnosed MTB cases as compared with both PPD+ (P < 0.01) and PPD- (P < 0.01) healthy controls, while no significant difference could be found in the percentages of T or NK cells among these groups. However, comparing recurrent cases with recently diagnosed cases showed a significant difference only in the percentage of T cells (P < 0.01). There was also a significant difference in the percentage of T cells according to severity of disease (P < 0.01) and in the association of diabetes mellitus (P < 0.01). Age, gender and treatment with antituberculosis chemotherapy had no effect on the percentages of T, NK or NKT cells. It is concluded that T and NKT cells play an important role in immunity against TB. In active pulmonary tuberculosis, increased T cell count points to severity of the disease, while their reduced count predicts bad prognosis. Human NKT cell count is a marker of disease activity. Enumeration of these cells in peripheral blood can be used as a non-invasive prognostic indicator for patients with active pulmonary TB.