Editors' ChoiceTuberculosis

Can Anti-Inflammatory Drugs Fight Infection?

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Science Translational Medicine  03 Jul 2013:
Vol. 5, Issue 192, pp. 192ec110
DOI: 10.1126/scitranslmed.3006879

Despite the availability of effective treatments, tuberculosis (TB) continues to be a major cause of illness and death worldwide. Illness from TB occurs when the immune system cannot control the bacterial pathogen Mycobacterium tuberculosis, resulting in lung lesions that contain this bacterium and immune cells. Current anti-TB therapy is challenging because patients must take antibiotics, which have side effects, for more than 6 months. Additional treatments that could decrease the duration of antibiotic therapy or improve the chance of cure would reduce the global burden of TB.

Vilaplana and colleagues hypothesized that inflammation is the key feature preceding lung lesion formation in TB infection. In a mouse strain not commonly used in TB research, they found that intravenous infection with a high dose of M. tuberculosis caused lung lesions 3 weeks later. In these mice, lung lesions rapidly increased in size, resulting in destruction of lung tissue, and were associated with weight loss and death. Three weeks after infection, they treated 18 mice with the anti-inflammatory drug ibuprofen. They compared the lungs of these animals to those of 18 untreated animals. They found an impressive decrease in the amount of lung tissue damage and in the number of M. tuberculosis bacteria in the lungs of treated animals. Last, they compared survival rates in 12 animals treated with ibuprofen 4 weeks after TB infection to that for untreated animals. They found that ibuprofen increased survival, with half of treated animals alive at day 50 as compared with <20% of untreated animals. None of the mice received standard anti-TB therapy.This study suggests that, in an animal model of TB infection, inflammation is an important player in determining the progression of lung lesions. Use of an inexpensive, widely available, commonly used anti-inflammatory drug can reduce the progression of lung lesions and reduce lung tissue damage. Whereas the report by Vilaplana et al. is an important first step toward considering the use of ibuprofen in human TB infection, additional studies are needed to inform the dose and timing of anti-inflammatory drug treatment in conjunction with standard anti-TB therapy in human clinical trials.

C. Vilaplana et al., Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis. J. Infect. Dis. 208, 199–202 (2013). [Full Text]

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