This is what we claim in our just released manuscript, published in JID (Ibuprofen is able to reduce the lung pathology, to decrease bacillary load in tissues and to increase survival in a new murine experimental model of active tuberculosis
Cristina Vilaplana; Elena Marzo; Gustavo Tapia; Jorge Diaz; Vanesa Garcia; Pere-Joan Cardona
Journal of Infectious Diseases 2013; doi: 10.1093/infdis/jit152)
Trying to discern the transformation of Latent TB into cavitation in the context of fibrotic response found in the human lung let us to the discover of ibuprofen as a clue treatment and prevention against TB.
Five years ago, we ask ourselves how the tiny lesions existing in Latent TB can become a cavity? As seen in the minipig model, the lesions in LTBI are characterized by an early encapsulation because of the septae wich structure the lungs in big mammals (GilPLOSOne_2010_TB_minipigs). In this scenario the development of cavitary lesions -which requires a minimal size of 20mm- appears to be impossible. In this process, the softening of the necrotic tissues appear to be paramount, and that’s why -recalling previous experiences with SCID mice model treated with Ab (Guirado, Passive Serum Therapy, MicInfect 2006)- we looked after different necrotic models in mice, as C3HeB/FeJ.
Starting its characterization (Marzo et al, manuscript submitted) we saw the clue was the high neutrophilic infiltration which occur in the lesions when compared to other mouse strains. This, together with undergoing coalescence with neighbouring lesions (coalescence theory), made possible the sudden exponential increase of their size from week 3 post infection. This could easily be what happens in the upper lobes of the lung, where there is a low density of the capillary net allowing a poorer drainage of the bacilli.
Focusing into the neutrophilic infiltration instead of the softening process, we decided to study the effect of common (and cheap!) anti-inflammatories like ibuprofen or aspirin in the course of TB disease. The results showed that the decrease of the inflammatory response leaded to a reduction of the bacillary load and a significant increase of the survival of the animals.
These results highly support the idea of the introduction of ibuprofen in the treatment of active TB could be very benefitial to the patients, specially for those suffering from MDR/XDR, which have no other hope.
For all this, we strongly ask for scientists to perform Phase III Clinical Trials able to directly assess this effect in humans. Moreover, observational studies could be also be needed to compare the incidence of TB in different cohorts -currently treated or not with low-dose aspirin, for example patients suffering of diabetis or a cardiac situation requiring anti-aggregation treatment.
This work was finantially supported by the ISCIII through the FIS 11/01702 and CIBERES CPR-TB. The results have been published in the Journal of Infection Diseases, and you can access the manuscript here.