Chronic obstructive pulmonary disease
Host genotype-specific therapies for tuberculosis
This paper suggests that therapies for tuberculosis (TB) will, in the future, be tuned
specifically to the patient’s genotype. Using zebra fish and human models, Tobin et al
demonstrated that susceptibility to TB can be caused by both reduced and increased
inflammatory activity, which in turn is governed by the patient’s genotype. The increased
inflammatory pathway begins with increased leukotriene A4 hydrolase (LTA4H) activity,
which leads to increased production of a proinflammatory eicosanoid (LBT4) and tumour
necrosis factor. The decreased inflammatory pathway begins with reduced LTA4H activity
resulting in increased anti-inflammatory activity and increased production of lipoxins. Both
mechanisms cause lysis of macrophages.
These findings suggests that by identifying whether a patient infected with TB is in a high
or reduced inflammatory state, as dictated by their LTA4H genotype and the detrimental
effects of each extreme countered, patient morbidity and mortality would be improved.
Blindly used ‘scatter-gun’ therapies may be either beneficial or detrimental, depending on the
inflammatory state of the patient. In the increased inflammatory state produced by increased
LTA4H activity, targeted therapies, such as aspirin, may be useful as this inexpensive drug
inhibits tumour necrosis factor activity. Similarly, in those with a reduced inflammatory state
(the low-activity LTA4H genotype) limiting the increased anti-inflammatory activity may be
The development of genotype-directed treatment strategies for TB and other serious
infections will be an interesting area of future research.
infections. Cell 2012;148:434e46.
Tobin DM, Roca FJ, Oh SF, et al. Host genotype-specific therapies can optimize the inflammatory response to mycobacterial
Correspondence to Dr Joanna Devlin, CT2, Royal Hampshire County Hospital, Romsey Road, Winchester, Hampshire SO22
5DG, UK; firstname.lastname@example.org
Thorax December 2012 Vol 67 No 12
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