Cytokine production and polymorphisms in the IFN gamma, IFN gamma R1 and IL12 genes

Lavanya Joshi; Lakshmi Kiran Chelluri; Sumanlatha Gaddam

Lavanya Joshi research associate
Lakshmi Kiran Chelluri Global Hospitals, Hyderabad, India
Sumanlatha Gaddam Department of Genetics, Osmania University, Hyderabad, India

Keywords: Household contacts; Single nucleotide polymorphisms; IL-12/IFN-?; IFNgR1, cytokine secretion.

Abstract

One third of the world's current population has been infected with Mycobacterium tuberculosis. However, most of these cases will not develop the full-blown active disease and remain asymptomatic, known as latent tuberculosis infection (LTBI). Although the LTBI individuals are asymptomatic, there is a chance of reactivation and 5-10% of them develop active tuberculosis (TB). The risk of reactivation is high among the household contacts of active TB. Thus, household contacts constitute an important target for early prevention and control of tuberculosis. Cytokines play an important role in protective immunity and may aid in identification of diagnostics and new vaccines. The role of IL-12 and IFN-? has been established in protection against mycobacterial infections. The balance between the secretions of IL-12/IFN-? appears to be essential for the regulation of inflammation in response to Mycobacterium tuberculosis. The aim of the present study was to evaluate the cytokine production in serum and culture supernatants and the single nucleotide polymorphisms (SNPs) in the IFN-? and IL-12 genes.

The cytokine levels of IFN- ? and IL-12 were estimated in serum (n=150) and culture supernatants (n=25) stimulated with r32kda Mycobacterium bovis BCG in active pulmonary tuberculosis patients (APTB), household contacts (HHC) and healthy controls (HC) by enzyme-linked immunosorbent assay (ELISA) and their genetic polymorphisms (n=150) were studied by amplification refractory mutation systems polymerase chain reaction (ARMs PCR).

The mean serum levels of IFN- ? and IL12 were high in APTB and HHC compared to HCs. The mean stimulated levels of IFN-? were significantly low in APTB and HHC compared to HC. IL-12 cytokine levels were significantly high in APTB and HHC as compared to HCs. The AT genotype in IFN-? +874 A/T, CC and TC genotypes in IFNgR1-56C/T were found to be associated with TB. In conclusion, cytokine levels and cytokine gene polymorphisms affect the susceptibility to tuberculosis in household contacts.