Adjunctive TNF inhibition with standard treatment enhances bacterial clearance in a murine model of necrotic TB granulomas.
PLoS One
; 7(6): e39680, 2012.
Article
en En
| MEDLINE
| ID: mdl-22761866
ABSTRACT
BACKGROUND:
It has been hypothesized that early host-responses during TB treatment may paradoxically promote survival of persistent bacteria. We therefore evaluated whether adjunctive inhibition of tumor necrosis factor alpha (TNF-α)-a key cytokine in host responses against TB-could hasten bacterial clearance in a mouse strain that develops necrotic lesions in response to Mycobacterium tuberculosis infection. METHODOLOGY/PRINCIPALFINDINGS:
Six weeks after an aerosol infection, C3HeB/FeJ mice received standard TB treatment with or without adjunctive TNF inhibition (etanercept for the initial six weeks). Functional TNF-α levels and lung pathology were found to be reduced in the mice receiving etanercept. Compared to standard TB treatment, the addition of etanercept resulted in a significantly lower pulmonary bacterial burden, corresponding to the phase when a significant proportion of bacteria are multiplying slowly (p<0.0233). Finally, only 10.5% of mice receiving adjunctive etanercept versus 27.8% receiving standard TB treatment alone relapsed.CONCLUSION:
This study provides proof-of-principle that modulation of TNF-α activity can hasten bacterial clearance during standard multi-drug TB treatment. Oral agents that modulate TNF-α should therefore be considered as adjunct therapies for shortening TB treatments. However, due to concerns of reactivation disease, additional studies need to be performed before TNF-α inhibitors are used for TB treatment in humans.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tuberculosis
/
Inmunoglobulina G
/
Factor de Necrosis Tumoral alfa
/
Receptores del Factor de Necrosis Tumoral
/
Modelos Animales de Enfermedad
/
Granuloma
/
Mycobacterium tuberculosis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos