Elevated Levels of Interferon-inducible Protein-10 (IP)-10/CXCL10, but not of Interferon-gamma, in Patients with Pulmonary Tuberculosis

ABSTRACT

Mycobacterial strains are potent inducers of cytokines/chemokines by mononuclear phagocytes, which constitute an important cellular component of the first line of defense in the innate immune system. Interferon (IFN)-gamma-inducible protein (IP-10 or CXCL10) is a potent chemoattractant; however, little is known about the IP-10 profiles attributable to the Th1 regulation associated with active tuberculosis (TB). In this study, we investigated the production of IP-10, interleukin (IL)-12 p40, and IFN-gamma by the peripheral blood mononuclear cells (PBMCs) of patients with active pulmonary TB in response to in vitro stimulation with Triton X-100 soluble proteins (TSPs) or the 30-kDa antigen. The TSP antigens used in the present study were isolated and purified from Mycobacterium tuberculosis H37Rv (virulent strain), M. tuberculosis H37Ra (avirulent strain), and Mycobacterium bovis BCG. The results were compared with those obtained for healthy tuberculin reactors (HTRs). Concordant with earlier studies, IFN-gamma production was significantly depressed in the PBMCs from TB patients compared with those in the HTR group. However, the IP-10 levels in the PBMCs from TB patients were significantly elevated 18 h after stimulation compared to those in the PBMCs from HTRs. IP-10 release was correlated in a significant manner with the release of IFN-gamma in the HTRs, but this was not the case for the TB patients. Collectively, these data suggest that TB patients show altered regulation of Th1-driving cytokine and chemokine production in response to a variety of mycobacterial antigens.