Immunotherapy of Airborne Tuberculosis in Mice Via the Lung-specific Delivery of Cytokines

The immunotherapeutic potential of interleukin-2 (IL-2), tumour necrosis factor alpha (TNFα) and interferon gamma (IFN-γ) administered by aerosol was examined on mice infected with Mycobacterium tuberculosis by the aerogenic route. Infection of balb/c mice with 10(4) colony forming units (cfu) of M tuberculosis led to death of all mice at day 35 post infection after progressive microbial growth in the lungs. Aerosolization of IL-2 (100 μg per mouse) did not promote an increase in resistance to tuberculosis, as seen by growth of M tuberculosis in the lungs. Administration of IFN-γ or TNFα (100 μg) by the aerosol route led to a significant reduction in microbial growth in the lungs and a 100% survival of infected mice at day 60. Similarly, aerosolization of TNFα and IFN-γ combined led to a very high degree of tuberculostatic activity in the lungs of infected animals, but not superior to that seen with either cytokine alone. Administration of similar amounts of cytokines by repeated intraperitoneal infusions led to a very marginal improvement in mouse resistance. These results suggest that localized cytokine administration may be beneficial in the treatment of lung diseases.