Tuberculosis Research

We pioneered bronchoalveolar lavage studies in patients with active pulmonary TB showing increases in inflammatory cytokines, the role of Th1 responses in the lung, adhesion molecules in granuloma formation, and increased matrix metalloproteinase’s leading to cavity formation. Alveolar macrophages down regulate inhibitory C/EBP ß and up regulate NF-RB in these inflammatory disorders. We showed a deficiency of interferon-γ in BAL and augmented this with a pharmacologic aerosol in MDR-TB with sputum conversion in 5/5 patients. Interferon-γ induced STAT-1 and IRF-1 and 9. In a randomized controlled clinical trial of 96 cavitary TB patients in Cape Town interferon-γ aerosol added to DOTS significantly accelerated sputum conversion, reduced respiratory symptoms, and inhibited inflammatory cytokines released by BAL cells. Current research is on TB/HIV interaction in BAL cells, prevention and treatment of IRIS by interferon-γ, and evaluating alveolar macrophage transcription factors.