Immune regulation in multiple sclerosis : cytokines and metalloproteinases

Immunological mechanisms play a central role in the pathogenesis sclerosis (MS). In this study two groups of related immune variables are cytokines and metalloproteinases (MMPs), which regulate each other's production and activation. Cytokines play key role in pathogenesis and treatments of Cytokines are regulatory proteins secreted by a variety of cells. The pleiotropic action of cytokines include numerous effects on cells of the immune modulating immune responses. Cytokine receptors are crucial for the net effect of cytokines. The balance between Th1 and Th2 type cytokines might determine whether the immune response in MS is detrimental or beneficial. MMPs are a group of endopeptidases that degrade extracellular pro mechanisms in the genesis of inflammatory demyelination, such as recruitment, blood-brain barrier breakdown and myelin destruction are con be MMP-dependent processes. Aims of the study: 1. To investigate the levels of cytokine secreting blood and cerebrospinal fluid mononuclear cells (MNC) in patients with MS and controls; 2. To define further the cytokine disbalance in MS by examining the levels of cytokine receptors that are important in the net effect of cytokine function; 3. To study the levels of blood and CSF MNC in MS expressing mRNA of MMPs and their inhibitors; and 4. To examine the effects of IFN-[beta] on cytokines and MMPs in MS. Results: MS is associated with increased numbers of IL-6 and TNF-[alpha] secreting blood MNC and decreased numbers of IL-10 secreting cells compared to healthy subjects. In CSF, similar numbers of IL-6 and IL-10 secreting cells were observed in patients with MS and other neurological diseases (OND). Patients with MS also had higher levels of MMP-3, MMP-9 and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA expressing blood MNC compared to controls. When patients with MS examined before vs. during 1 year of treatment with IFN-[beta], treatment resulted in decreased numbers of IL-6 and TNF-[alpha] secreting MNC