A role for interferon-beta in Guillain-Barré Syndrome?

Autor(es): Créange A

Resumo: Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating neuropathy that is associated with long-lasting morbidity and a substantial risk of mortality. The 2 reference treatments, plasma exchange and intravenous immunoglobulins (IVIg), do not change the functional prognosis for the most severely ill patients. The pathogenesis of GBS involves humoral and cellular immune dysfunctions that have only recently been characterised. Antibodies to nerve antigens may participate in complement activation, antibody-dependent macrophage cytotoxicity and reversible conduction failure. The cellular immune reaction is associated with increases in pro-inflammatory cytokines [such as tumour necrosis factor-alpha (TNFalpha)] and matrix metalloproteinases (MMPs; e.g. MMP-9), and a decrease in anti-inflammatory cytokines [such as transforming growth factor-beta1 (TGFbeta1)]. All the changes favour adhesion to and transmigration across the endothelium of immune cells, a key phenomenon associated with GBS. Recovery from GBS is characterised by the normalisation of these changes. Experimental allergic neuritis (EAN), the experimental model of GBS, has strikingly similar immunological characteristics. The usual treatment options for patients with GBS (plasma exchange and IVIg) mainly target the humoral component of the immune response. Interferon-beta (IFNbeta) is a cellular immunomodulator that inhibits antigen presentation and TNFalpha production and binding, and modulates macrophage properties. IFNbeta increases anti-inflammatory T cell functions and the production of anti-inflammatory cytokines, such as TGFbeta1. IFNbeta has important effects on leukodiapedesis, caused by modulating the expression of cell adhesion molecules and the MMP-9 proteinases. It has been used with success in EAN, in some patients with acute exacerbation of chronic inflammatory demyelinating polyneuropathy, and in 1 patient with GBS. The pathophysiology of patients with GBS, an understanding of IFNbeta properties and results of experimental studies support the investigation of IFNbeta in trials of patients with GBS.

Imprenta: BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy, v. 14, n. 1, p. 1-11, 2000

Descritores: Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Immune response ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Antibodies ; Guillain-Barre Syndrome - Cytokines ;

Data de publicação: 2000