¿Ibuprofeno o aspirina……..

en el tratamiento de la TB?

www.unitatdetuberculosiexperimental.wordpress.com

?

(x10 of the real size)

THE QUESTION

THE ANSWER:

because of the Coalescence theory

Because Laennec said it (XIX)….and we have seen it.

HOW DO WE KNOW?

because of the model

C3HeB/FeJ !!!

HOW DO WE KNOW?

because of the model

Marzo et al, Tuberculosis 2013; http://dx.doi.org/10.1016/j.tube.2013.09.004

THE COALESCENCE THEORY

0,5 mm Ø, d21

2 mm Ø, d301 mm Ø, d28

(x10 of the real size)

8 mm Ø, d33

HOW DO WE KNOW?

because of the model

Marzo et al, Tuberculosis 2013;

http://dx.doi.org/10.1016/j.tube.2013.09.004

Necrosed neutrophils

d21 d28

intraalveolar

acellular product

Big lesions

Central necrosis

Caseous necrosis

towards

liquefactive

necrosis

Bacilli in the

neutrophilic regions

…and in the

necrotised regions

Neutrophils

TB IS DUE TO A FIBROSIS-

ANTIFIBROSIS IMBALANCE

TB IS DUE TO A

FIBROSIS-ANTIFIBROSIS IMBALANCE

HEPARIN WORKS NOT BECAUSE ITS EFFECT ON

FIBROSIS BUT FOR IS ANTI-INFLAMMATORY

EFFECT

Bleomycin: induces fibrosis

Doxycyclin: inhibits MMP (involved in collagen degradation)

Heparin: antifibrotic effect

THE ORIGIN OF THE IDEA

ACTIVE TB IS AN INFLAMMATORY DISEASE

LET’S TRY ANTI-INFLAMMATORIES

WHICH ONES??

THE RESULTS

Control Ibuprofen

THE RESULTS

Vilaplana et al, Journal of Infectious Diseases 2013; doi: 10.1093/infdis/jit152)

LUNG PATHOLOGY BACILLARY LOAD SURVIVAL

pro-inflammatory mediators: TNF-α, IL-17, IL-6 and CXCL5

Marzo et al, Tuberculosis 2013 http://dx.doi.org/10.1016/j.tube.2013.09.004

THE RESULTS

0.5 mm Ø, d21

2 mm Ø, d301 mm Ø, d28

8 mm Ø, d33

THE WAY WE DO THINK IT WORKS

EncapsulationEncapsulationEncapsulationEncapsulation

0.5 mm Ø, d21

1 mm Ø, d28

0.5 mm Ø, d33

THE WAY WE DO THINK IT WORKS

Common anti-inflammatories are:

CHEAP ALREADY IN THE MARKETSAFEWIDELY AVAILABLE (WHO essential medicines)

WHY IS THIS IMPORTANT FOR TB PATIENTS?

THEY ARE READY TO BE USED

These results in mice encourage to use them as a COADJUVANT together with standard anti-TB treatment. Its use should ameliorate both the disease course and its outcome.

NEXT STEPS

STUDY IN SPAIN

(UITB+SEPAR+UTE: MIQUEL SERVET)

STUDY IN MOZAMBIQUE + SOUTH AFRICA(CISM+PHRU+UTE: EDCTP)

STUDY IN ANGOLA(VHIR+UTE: ?)

You are very welcome to present your ideas and collaborations!

PLEASE THINK ABOUT IT

THE PEOPLE

www.unitatdetuberculosiexperimental.wordpress.com