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Vol. 5. Issue 1.
Pages 34-39 (January - February 2009)
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Vol. 5. Issue 1.
Pages 34-39 (January - February 2009)
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Interleukin 6 in the Physiopathology of Rheumatoid Arthritis
La interleucina 6 en la fisiopatología de la artrirtis reumatoide
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José Luis Pablos Álvarez
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jlpablos@h12o.es

Correspondence author.
Servicio de Reumatología y Unidad de Investigación, Hospital 12 de Octubre, Madrid, Spain
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Abstract

Interleukin (IL) 6 was identified in 1986 as a factor produced by T lymphocytes, that mediates growth and immunoglobulin synthesis on B lymphocytes. IL-6 is a member of a large cytokine family sharing a gp130 membrane receptor. This receptor mediates specific Jak/STAT3 activation, which induces widespread expression of pro-inflammatory and immunoregulatory genes. IL-6 mediates potent systemic responses, in organs distant from its local inflammatory sources, in a prominent fashion compared to other cytokines. Most specific effects involve hematopoiesis and hepatic acute phase reactants synthesis. IL-6 became a rheumatoid arthritis (RA) target due to its pro-inflammatory and joint destructive potential, as well as its participation in T and B immunoregulation. The therapeutic success of tocilizumab has confirmed IL-6 as an RA target.

Although additional studies on the participation of IL-6 in RA physiopathology are needed, a number of indirect data point to a relevant position in this setting.

Keywords:
Interleukin 6
Cytokines
Rheumatoid arthritis
Physiopathology
Therapy
Tocilizumab
Resumen

La interleucina (IL) 6 fue identificada en 1986 como un factor producido por los linfocitos T, con efectos estimuladores del crecimiento y síntesis de inmunoglobulinas en los linfocitos B. Pertenece a una amplia familia de citocinas que comparten el receptor de membrana gp130, mediador de una señal específica de activación del sistema Jak/STAT3 con amplios efectos en la expresión de genes proinflamatorios e inmunorreguladores.

De forma más prominente que otras citocinas, la IL-6 media potentes acciones sistémicas en órganos distantes de su origen local inflamatorio. Las más específicas afectan a la hematopoyesis y la síntesis hepática de reactantes de fase aguda. Su potencial actividad proinflamatoria y de destrucción articular, junto con su implicación en la inmunorregulación T y B, la convirtió en una diana terapéutica atractiva, confirmada por el éxito de su antagonista tocilizumab en la artritis reumatoide (AR).

Aunque son necesarios estudios más amplios sobre la participación de la IL-6 en la fisiopatología de la AR, numerosos datos indirectos permiten situarla en una posición muy relevante.

Palabras clave:
Interleucina 6
Citocinas
Artritis reumatoide
Fisiopatología
Terapia
Tocilizumab
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