More MS news articles for August 2002

Proteolytic balance in patients with multiple sclerosis during interferon treatment

J Interferon Cytokine Res 2002 Jun;22(6):689-92
Giannelli G, De Marzo A, Scagnolari C, Bergamini C, Fransvea E, Bagnato F, Bellomi F, Millefiorini E, Gasperini C, Antonaci S, Antonelli G.
Department of Internal Medicine, Immunology, and Infectious Diseases, Section of Internal Medicine, University of Bari Medical School, Bari, Italy.

Multiple sclerosis (MS) is a progressive, inflammatory, demyelinating disease.

An altered cytokine network has been reported to occur during the disease, and its pathogenetic role has been hypothesized.

To date, interferon-beta (IFN-beta) is the most effective and reliable therapy in the majority of MS patients, although the mechanisms underlying its therapeutic effects are not fully understood.

Breakdown of the blood-brain barrier (BBB) with consequent extravasation of the T cells and their invasion of the brain parenchyma seems to be one of the most important steps in the pathogenesis of the disease.

Matrix metalloproteinease-2 (MMP-2) and MMP-9 are enzymes with proteolytic activities toward extracellular matrix ECM components.

They are physiologically balanced by the MMP tissue inhibitors TIMP-2 and TIMP-1, so that proteolysis occurs as the result of increased MMP or decreased TIMP levels.

In 38 patients with MS, MMP-2 and TIMP-1 levels were similar before and after 9 months of IFN-beta therapy, whereas MMP-9 levels significantly decreased and TIMP-2 levels significantly increased in comparison to values obtained before treatment.

These results suggest that IFN-beta modulates T cell activities, including MMP and TIMP production, thus contributing either to maintaining the integrity of the BBB or to slowing the progression of the disease.