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Vol. 38. Issue 7.
Pages 311-316 (July 2002)
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Vol. 38. Issue 7.
Pages 311-316 (July 2002)
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Expresión de los genes de la interleucina 10 (IL-10) y del factor de necrosis tumoral alfa (TNF-α) en músculos respiratorios y periféricos. Relación con el daño sarcolémico
Interleukin 10 and tumor necrosis factor alpha gene expression in respiratory and peripheral muscle. Relation to sarcolemmal damage
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J. Palacioa,
Corresponding author
jgea@imim.es

Correspondencia: Dr. J. Gea. Servicio de Neumología. Hospital del Mar.P.° Marítim, 27. 08003 Barcelona
, J.B. Gáldizb, J.J. Bechc, M. Mariñánb, C. Casadevalla, P. Martínezc, J. Geaa
a Servicio de Neumología. Unidad de Investigación Respiratoria y Ambiental. Hospital del Mar. IMIM. Fisiopatología (CEXS). Universitat Pompeu Fabra. Barcelona
b Servicio de Neumología. Hospital de Cruces. Universidad del País Vasco. Bilbao
c Unidad de Inmunología.Instituto de Biotecnología y Biomedicina. Universitat Autònoma de Barcelona. Barcelona
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Antecedentes

El factor de necrosis tumoral alfa (TNF-a) se ha implicado en la pérdida de masa muscular en la enfermedad pulmonar obstructiva crónica (EPOC) y otras enfermedades consumtivas. Su producción estaría en relación con la inflamación derivada de la propia enfermedad pulmonar o el hábito tabáquico, llegando al músculo por el torrente sanguíneo. Sin embargo, también se ha sugerido que el TNF-α podría expresarse directamente en el tejido muscular. Sea cual fuere el lugar de producción, la relación del TNF-α con el daño muscular subsiguiente no es clara

Objetivo

Hemos estudiado la expresión del TNF-α y una interleucina inhibidora de su producción (IL-10) en los músculos respiratorios principales y en un músculo periférico del perro

Métodos

Se han incluido nueve animales machos, adultos jóvenes de raza Beagle. En todos ellos se tomaron biopsias del diafragma (Df), del intercostal externo (IExt) y de un músculo de las extremidades (vasto interno del cuádriceps o VInt). Se analizó la expresión de los genes de TNF-α e IL-10, a través de la determinación de sus ARNm corres-pondientes, utilizando la transcripción reversa y reacción en cadena de la polimerasa (RT-PCR). También se evaluó el daño sarcolémico mediante detección de fibronectina intra-celular (inmunohistoquímica)

Resultados

Los valores de expresión de ambas citocinas evidenciaron una amplia dispersión interindividual. Por un lado, la expresión de TNF-α fue mínima en Df y IExt (respectivamente, 0,02 ± 0,03 y 0,05 ± 0,06 u.a.), con valores relativamente elevados en VInt (0,14 ± 0,08 u.a.). A su vez, la IL-10 evidenciaba valores bajos en DF (0,6 ± 0,5 u.a.), que eran algo superiores en IExt (2,7 ± 1,9 u.a.; p < 0,01) y VInt (1,6 ± 1,7 u.a.). El daño sarcolémico era mínimo en los tres músculos y se relacionaba con la expresión de TNF-α en el músculo periférico (r=0,682; p < 0,05)

Conclusiones

a) TNF-α e IL-10 parecen expresarse constitutivamente en el músculo esquelético canino; b) los valores basales de expresión del TNF-α son menores en los músculos repiratorios que en los de las extremidades mos-trando relación en estos últimos con el daño de membrana

Palabras clave:
Músculos respiratorios
Músculos periféricos
Citocinas
Background

Tumor necrosis factor alpha (TNF-α) has been implicated in loss of muscle mass in chronic obstructive pulmonary disease and other consumptive processes. TNF-α production would be related to inflammation arising from pulmonary disease itself or, alternatively, from smoking, and would be carried to the muscle through the blood stream. However, it has also been suggested that TNF-α may be expressed directly in muscle tissue. Regardless the site of production of TNF-α, its relation to subsequent muscle damage is unclear

Objective

We studied the expression of TNF-α and an interleukin inhibitor of its production (IL-10) in the main respiratory muscles and a peripheral muscle in the dog

Method

Nine young, male Beagle dogs were included. From all animals we obtained a biopsy of the diaphragm (Dph) and external intercostal (ExtI) muscles and a leg muscle (internal vastus of the quadriceps, IntV). TNF-α and IL-10 gene expressions were measured through the analysis of mes-senger RNA levels, using reverse transcription and polymera-se chain reaction. We also assessed sarcolemmal damage using intracellular fibronectin detection (immunohistochemistry)

Results

The expression of both cytokines showed wide in-terindividual variability. On the one hand, TNF-α (was very low in Dph and ExtI (0.02 ± 0.03 and 0.05 ± 0.06 a.u., respec-tively), but relatively high in the IntV (0.14 ± 0.08 a.u.). IL-10 expression, on the other hand was low in the Dph (0.06 ± 0.05 a.u.) and slightly higher in the ExtI (2.7 ± 1.9 a.u., p < 0.01) and IntV (1.6 ± 1.7 a.u.). Sarcolemmal damage was minimal in all three muscles and was related to TNF-α expression in the peripheral muscle (r=0.682, p < 0.05)

Conclusions

1) TNF-α and IL-10 appear to be constitutively expressed within the skeletal muscle in dogs. 2) Basal TNF-α expression is lower in respiratory muscles than in peripheral muscles. 3) The expression in the latter is related to membrane damage

Keywords:
Respiratory Muscles
Peripheral Muscles
Cytokines
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