Immune approaches in tuberculosis therapy: a brief overview

Abstract

TB is typically caused by Mycobacterium tuberculosis, a symbiotic bacterium present in one-third of the world’s population. There any many factors triggering overt clinical disease in a small proportion of humans. In our view the major role in the process is played by the host’s immune response, especially self-directed, destructive inflammation. Conventional chemotherapy produces bactericidal or bacteriostatic effects, but immunopathological changes can only be corrected by immunotherapy. Various attempts have been made to identify the optimal immune intervention. Some have shown promising effects, but many have failed. It is commonly believed that the field started in 1890: the year Robert Koch announced his tuberculin therapy. In the Pên Ts’ao Kang Mu, classical Chinese materia medica, published during Ming dynasty, Li Shi Chen (1518–1593) recommended, as a remedy for hemoptysis, to collect from the sputum “…blood lumps, roast them till they are black, and take then them as a powder”. In retrospect, this is perhaps the earliest recorded reference relating to immunotherapy of TB with heat-killed mycobacteria. Modern science is obviously geared toward more palatable approach, but without hindsight from often disdained empirical evidence no progress can be made. The clinical experience from various trial and error processes is briefly discussed in this review.

Keywords::

• AIDS
• antibody
• autoimmune
• cytokine
• HIV
• immunomodulator
• inflammation
• lung
• multidrug-resistant TB
• mycobacterial
• pulmonary
• therapeutic vaccine
• tubercle bacillus
• tuberculin

Acknowledgements

We would like to thank the many experts who have contributed their comments and critiques. In particular, we are indebted to John Stanford, Graham Rook, John Grange, Ali Zumla, Gene Shearer, Feng-li Tao, Shilong Yang, Jiang Pu, Chuanyou Li, Wing-wai Yew, CC Leung, Ying Zhang, Satoshi Makino, Ray Spier, Nataliya Kozhan, Vasilyi Petrenko, Elena Rekalova, Irina Il’inskaya, Petr Rytik, Felix Ershov, Volodymyr Pylypchuk, Pere-Joan Cardona, Jim Johnston, Carl Feng, Christoph Lange, Bob Wallis, Keertan Dheda, Gavin Churchyard, Tony Hawkridge, Tom Evans, Robert Loddenkemper, Stefan Kaufmann and Mel Spigelman for sharing with us their views on TB issues. The authors are also grateful to patients who participated in trials of immunotherapeutics discussed in this review.

Financial & competing interests disclosure

AS Bourinbaiar and V Jirathitikal are officers of the Immunitor company, involved in developing TB immunotherapies. Some of the trials of immunotherapeutics described in this review were supported by Business Partnership Grant UKB1-9017-LK-09 awarded by the US Civilian Research & Development Foundation – a nonprofit organization authorized by the US Congress and established in 1995 by the National Science Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.