AUTHOR=Kroesen Vera Marie , Rodríguez-Martínez Paula , García Eric , Rosales Yaiza , Díaz Jorge , Martín-Céspedes Montse , Tapia Gustavo , Sarrias Maria Rosa , Cardona Pere-Joan , Vilaplana Cristina 

TITLE=A Beneficial Effect of Low-Dose Aspirin in a Murine Model of Active Tuberculosis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00798

DOI=10.3389/fimmu.2018.00798

ISSN=1664-3224

ABSTRACT=An excessive, non-productive host-immune response is detrimental in active, chronic TB disease as it typically leads to tissue damage. Given their anti-inflammatory effect, NSAIDs can potentially attenuate excessive inflammation in active TB disease.
As such, we investigated the prophylactic and therapeutic effect of low-dose aspirin (3 mg/kg/d), either alone or in combination with common anti-TB treatment or BCG-vaccination, on disease outcome in a experimental murine model of active TB. Survival rate, bacillary load in lungs and lung pathology were measured. The possible mechanism of action of low-dose aspirin on the host’s immune response was also evaluated by measuring levels of CD5L/AIM, selected cytokines/chemokines and other inflammatory markers in serum and lung tissue. Low-dose aspirin increased survival, had anti-inflammatory effects, reduced lung pathology and decreased bacillary load in late-stage TB disease.  Moreover, in combination with common anti-TB treatment, low-dose aspirin enhanced survival and reduced lung pathology. Results from the immunological studies suggest the anti-inflammatory action of low-dose aspirin at both a local and a systemic level. Our results showed a systemic decrease in neutrophilic recruitment, decreased levels of acute-phase reaction cytokines (IL-6, IL-1 and TNF-) at late stage and a delay in the decrease in T cell response (in terms of IFN-, IL-2 and IL-10 serum levels) that occurs during the course of M. tuberculosis infection. An anti-inflammatory milieu was detected in the lung, with less neutrophil recruitment and lower levels of tissue factor. In conclusion, low-dose aspirin may be beneficial as an adjunct to standard anti-TB treatment in the late stage of active TB by reducing excess, non-productive inflammation, while enhancing Th1-cell responses for elimination of the bacilli.