Apoptosis linfocitaria y efecto inmunomodulador de interferón beta en la esclerosis múltiple

Resum

Multiple sclerosis (MS) is a chronic demyelinating disease characterized by the presence of inflammatory cells in the central nervous system. Although the primary cause of MS is yet unknown, there are evidences that T and B lymphocytes play a pathogenic role in the development of the disease. The efficacy of IFN in the treatment of MS has been demonstrated but its mechanism of action remains unclear. There are few studies evaluating the role of IFN in the regulation of apoptosis of lymphocytes in MS and their results are contradictory. However, the real incidence of this cell death has not been determined. The objective of this work was to determine the apoptosis of peripheral blood lymphocytes from untreated patients with MS and evaluate its regulation during IFN therapy. Methods: Peripheral blood mononuclear cells were isolated from patients with MS and healthy controls and the apoptosis of lymphocytes was measured after 24 hours of culture by three independent methods: annexin-V binding determination, low molecular weigh DNA extraction and active forms of caspases detection. A follow-up study of the incidence of apoptosis was performed at 0, 1, 6 and 12 months of treatment with IFN. Results: T lymphocytes, but not B lymphocytes, from untreated patients with MS showed higher percentages of apoptotic cells than those from healthy controls. This increment was more pronounced in those patients who suffered more than 2 MS attacks in the 2 years before the study. IFN therapy induced a significant reduction in the proportion of T cells undergoing apoptosis, reaching normal values after 12 months of treatment. However, a transient increase in the percentages of apoptotic cells was observed during MS attacks in those patients who suffered MS attacks despite IFN therapy. Conclusions: The susceptibility to undergo apoptosis is increased in T lymphocytes from patients with MS. This increment of apoptosis is related to the activity of the disease and is normalised after 12 months of IFN therapy.