Proteolytic balance in patients with multiple sclerosis during interferon treatment.

Abstract

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.

• Authors: Gianluigi Giannelli, Anna De Marzo, Carolina Scagnolari, Carlo Bergamini, Emilia Fransvea, Francesca Bagnato, Francesca Bellomi, Enrico Millefiorini, Claudio Gasperini, Salvatore Antonaci, Guido Antonelli
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 22 Issue 6 Pg. 689-92 (Jun 2002) ISSN: 1079-9907 [Print] United States
• PMID: 12162880 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Proteins
• Tissue Inhibitor of Metalloproteinase-1
• Tissue Inhibitor of Metalloproteinase-2
• Interferon-beta
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Adolescent
• Female
• Humans
• Injections, Intramuscular
• Interferon-beta (administration & dosage, therapeutic use)
• Male
• Matrix Metalloproteinase 2 (blood)
• Matrix Metalloproteinase 9 (blood)
• Middle Aged
• Multiple Sclerosis, Relapsing-Remitting (enzymology, genetics, therapy)
• Recombinant Proteins (administration & dosage, therapeutic use)
• Tissue Inhibitor of Metalloproteinase-1 (blood)
• Tissue Inhibitor of Metalloproteinase-2 (biosynthesis, blood)