Cytokine-based approaches to the treatment of multidrug-resistant tuberculosis

The most disturbing aspect of the current epidemic of tuberculosis (TB) is the appearance of large numbers of strains of Mycobacterium tuberculosis th at are resistant to one or more of the first-line agents used to treat the disease. Mortality associated with a multidrug-resistant strain of tubercul osis (MDR-TB) infection is reported to be extremely high, in many cases no different from the mortality of tuberculosis in the pre-antibiotic era. Infection control measures have limited the spread of MDR-TB. However, many outbreaks over the last several years have created a large reservoir of MD R-TB infection. In order to treat the cases of MDR-TB that are occurring no w and which will undoubtedly occur in the future, new approaches to treatme nt will be needed. Recent research into the immunopathogenesis of tuberculosis has provided in sight into the important constituents of the host immune system needed to c ontrol the infection in vivo. These elements include CD4+ and CD8+ T cells as well as cytokines such as interferon gamma (IFN I), interleukin-12 (IL-1 2), and tumour necrosis factor (TNF). IL-2, LFN gamma and M. vaccae vaccination have all shown promising effects in small preliminary studies. Evidence suggests that TNF antagonists and IL -12 may also prove useful in the treatment of drug-susceptible TB and MDR-T B. Further studies are needed to determine the precise role of these recombina nt proteins in the treatment of TB.