Tuberculosis (TB) is a major health problem requiring sustained immunity to inhibit Mycobacterium tuberculosis growth and appropriate antimicrobial
therapy to prevent dissemination and drug resistance. Cell-mediated immune responses to M.
tuberculosis involve the activation of
cytokines such as
Tumor Necrosis Factor (TNF) which is critical for
granuloma formation and host resistance against TB. TNF inhibition, used as
therapy for the treatment of inflammatory diseases, disrupts
granuloma allowing replication of mycobacteria which may increase the efficacy of TB
chemotherapy. To test this hypothesis mice infected with M.
tuberculosis were treated with
isoniazid (INH) and
rifampicin (RMP) in the presence or absence of
Enbrel, a soluble
TNF receptor antagonist during three phases of M.
tuberculosis infection. Inhibition of TNF with
Enbrel augmented the efficacy of TB
chemotherapy as shown by enhanced mycobacterial clearance from the lung of acute and established
infection as well as in chronically infected mice. Furthermore, TNF inhibition significantly reduced lung pathology as compared to TB
chemotherapy alone. Therefore, the experimental data suggest that TB
chemotherapy may be more effective in the presence of a
TNF inhibitor, which may be relevant to eradicate mycobacteria during chronic M.
tuberculosis infection or reactivation.