A Beneficial Effect of Low-Dose Aspirin in a Murine Model of Active Tuberculosis
Kroesen, Vera Marie (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Rodríguez-Martínez, Paula (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
García, Eric (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Rosales, Yaiza (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Díaz, Jorge (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Martín-Céspedes, Montse (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Tapia, Gustavo (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Sarrias, Maria-Rosa (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Cardona, Pere-Joan (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Vilaplana, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)

Fecha:	2018
Resumen:	An excessive, non-productive host-immune response is detrimental in active, chronic tuberculosis (TB) disease as it typically leads to tissue damage. Given their anti-inflammatory effect, non-steroidal anti-inflammatory drugs can potentially attenuate excessive inflammation in active TB disease. As such, we investigated the prophylactic and therapeutic effect of low-dose aspirin (LDA) (3 mg/kg/day), either alone or in combination with common anti-TB treatment or BCG vaccination, on disease outcome in an experimental murine model of active TB. Survival rate, bacillary load (BL) in lungs, and lung pathology were measured. The possible mechanism of action of LDA 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. LDA 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, LDA enhanced survival and reduced lung pathology. Results from the immunological studies suggest the anti-inflammatory action of LDA 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-1β, and TNF-α) at late stage and a delay in the decrease in T cell response (in terms of IFN-γ, IL-2, and IL-10 serum levels) that occurs during the course of Mycobacterium tuberculosis infection. An anti-inflammatory milieu was detected in the lung, with less neutrophil recruitment and lower levels of tissue factor. In conclusion, LDA may be beneficial as an adjunct to standard anti-TB treatment in the later stage of active TB by reducing excess, non-productive inflammation, while enhancing Th1-cell responses for elimination of the bacilli.
Ayudas:	Ministerio de Economía y Competitividad CP13/00174 Ministerio de Economía y Competitividad CPII14/00021
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Aspirin ; Host-directed therapies ; Non-steroidal anti-inflammatory drugs ; Tuberculosis ; Mycobacterium tuberculosis ; Mouse model
Publicado en:	Frontiers in immunology, Vol. 9 (april 2018) , ISSN 1664-3224

DOI: 10.3389/fimmu.2018.00798
PMID: 29740435

12 p, 3.1 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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