BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is associated with substantial morbidity, despite drug therapy. Interferon-gamma, a cytokine produced mainly by CD4 T lymphocytes, can activate alveolar macrophages, important effector cells in host immunity against Mycobacterium tuberculosis. We investigated safety and tolerability of aerosolised interferon-gamma in patients with MDR-TB, and assessed its efficacy in terms of sputum-smear grades. METHODS: We did an open-label trial of aerosol interferon-gamma given to five patients with smears and cultures positive for pulmonary MDR-TB, despite documented adherence to therapy. The patients received aerosol interferon-gamma 500 micrograms three times a week for 1 month. Safety and tolerability were assessed, and, as well as routine clinical assessments, sputum samples for smear and culture were collected at entry and weekly. Computed tomography scans of the chest were done at baseline and after therapy ended. FINDINGS: Interferon-gamma was well tolerated by all patients. In all five, bodyweight stabilised or increased. Sputum acid-fast-bacillus smears became negative in all patients, and the time to positive culture increased (from 17 to 24 days, not significant), which suggested that the mycobacterial burden had decreased. The size of cavitary lesions was reduced in all patients, 2 months after treatment had ended. INTERPRETATION: Preliminary data suggest that aerosol interferon-gamma is a well-tolerated treatment that may be useful as adjunctive therapy in patients with MDR-TB who are otherwise not responding well to therapy.
BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is associated with substantial morbidity, despite drug therapy. Interferon-gamma, a cytokine produced mainly by CD4 T lymphocytes, can activate alveolar macrophages, important effector cells in host immunity against Mycobacterium tuberculosis. We investigated safety and tolerability of aerosolised interferon-gamma in patients with MDR-TB, and assessed its efficacy in terms of sputum-smear grades. METHODS: We did an open-label trial of aerosol interferon-gamma given to five patients with smears and cultures positive for pulmonary MDR-TB, despite documented adherence to therapy. The patients received aerosol interferon-gamma 500 micrograms three times a week for 1 month. Safety and tolerability were assessed, and, as well as routine clinical assessments, sputum samples for smear and culture were collected at entry and weekly. Computed tomography scans of the chest were done at baseline and after therapy ended. FINDINGS:Interferon-gamma was well tolerated by all patients. In all five, bodyweight stabilised or increased. Sputum acid-fast-bacillus smears became negative in all patients, and the time to positive culture increased (from 17 to 24 days, not significant), which suggested that the mycobacterial burden had decreased. The size of cavitary lesions was reduced in all patients, 2 months after treatment had ended. INTERPRETATION: Preliminary data suggest that aerosol interferon-gamma is a well-tolerated treatment that may be useful as adjunctive therapy in patients with MDR-TB who are otherwise not responding well to therapy.
Authors: Chad J Roy; Satheesh K Sivasubramani; Noton K Dutta; Smriti Mehra; Nadia A Golden; Stephanie Killeen; James D Talton; Badre E Hammoud; Peter J Didier; Deepak Kaushal Journal: Antimicrob Agents Chemother Date: 2011-12-05 Impact factor: 5.191
Authors: Dennis Montoya; Manali Mehta; Benjamin G Ferguson; Rosane M B Teles; Stephan R Krutzik; Daniel Cruz; Matteo Pellegrini; Robert L Modlin Journal: Immunology Date: 2018-11-11 Impact factor: 7.397