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 that are resistant to one or more of the first-line agents used to treat the disease. Mortality associated with a multidrug-resistant strain of tuberculosis (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 MDR-TB infection. In order to treat the cases of MDR-TB that are occurring now and which will undoubtedly occur in the future, new approaches to treatment will be needed. Recent research into the immunopathogenesis of tuberculosis has provided insight into the important constituents of the host immune system needed to control the infection in vivo. These elements include CD4+ and CD8+ T cells as well as cytokines such as interferon gamma (IFNgamma), interleukin-12 (IL-12), and tumour necrosis factor (TNF). IL-2, IFNgamma 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-TB. Further studies are needed to determine the precise role of these recombinant proteins in the treatment of TB.