Mycobacteria, cytokines and antibiotics.

We still do not understand the mechanism of immunity ty mycobacteria in man, and convincing reproducible kill of M. tuberculosis by human macrophages has not been achieved. The pathways so far elucidated, involving gamma interferon, 1,25(OH)2 vitamin D3, and TNF release seem more likely to lead to immunopathology than to protection. Meanwhile the major problem for the clinician is the existence of "persister" bacteria, which are not eliminated by the immune response, even when therapy has greatly reduced the bacterial load. It seems unlikely that it will be possible to design antibiotics which will rapidly kill dormant persister bacilli, so new strategies for therapy may need to concentrate on modulation of the host response. The objectives of such therapies would be: 1) "Reawakening" of dormant persisters. 2) Rapid immune recognition of persisters. 3) Suppression of the tissue-damaging pathway. 4) Enhancement of the optimally protective mechanism, but this has not yet been defined.