Differential Cytokine Response and IgG Subclasses in Pulmonary TB Patients, Household Contacts and BCG Vaccinated PPD-ve Healthy Controls

Abstract

Immune response to Mycobacterium tuberculosis is complex and some cytokines are believed to be involved in protective response in humans. In the present study the levels of IFNγ, IL-17, IL-10 and IL-2 stimulated by PPD and ESAT-6 in the PBMCs of active untreated pulmonary TB patients (PTB), their PPD+ve household contacts (HHC) and PPD-ve healthy controls (H) has been estimated at the start and 2 months and 6 months after the start of treatment. IgG subclass antibodies to ESAT-6 and Ag85 complex circulating in the serum of the study subjects on the same days were also measured. Significantly elevated levels of cytokines were secreted by the unstimulated PBMC of patients and HHC in comparison to healthy individuals. PPD significantly increased the secretion of all the measured cytokines by the PBMC of healthy individuals and patients. Higher levels of IL-2 and lower levels of IL-10 were secreted by the PBMC of healthy individuals than the patients whereas that between HHC and patients did not differ. Ratio of IFNγ/IL-10 was also compared among study subjects and significantly higher ratio was observed in healthy subjects than patients and HHC. Significantly higher IgG1 response to ESAT-6 and Ag85 complex was detected in patients' sera than HHC. No effect of treatment could be observed in cytokine and IgG1 levels in all the groups on all the days studied. Our findings suggest preactivated state of TB patients and their PPD+ household contacts and significant cellular immune reactivity by PPD-ve healthy individuals. Further, our findings suggest that IFNγ/IL-10 ratio could differentiate infection from cure.