**1. Introduction**

Around 2.8 million people are diagnosed with multiple sclerosis (MS) worldwide. MS is an autoimmune demyelinating disease of the central nervous system (CNS) of unknown etiology. Hallmarks of MS include focal inflammatory infiltrates, demyelinating plaques, reactive gliosis, and axonal damage [1, 2].

The mechanism of MS pathology involves complex interactions between systems and cell types including neurons, glia, and immune cells, accompanied by permeability of the blood–brain barrier (BBB). Autoreactive T cells activated outside the CNS cross the BBB and are reactivated by local antigen-presenting cells. Secretion of proinflammatory cytokines stimulates microglial cells and astrocytes, recruits additional inflammatory cells, and induces antibody production by plasma cells [3].

Recombinant interferon-β (IFN-β) remains the most widely prescribed treatment for relapsing–remitting MS (RRMS) and a valid approach because of its good benefit/risk profile. Despite widespread use of IFN-β, its therapeutic mechanism is still partially understood. The efficacy of IFN-β treatment has been shown by a decreased annual relapse rate, disability progression and inflammatory brain lesions resulting in the approval of different IFN-β preparations [4].

IFN-β is a highly pleiotropic cytokine which antagonizes the proinflammatory milieu by inhibiting expression of proinflammatory molecules, while increasing production of anti-inflammatory factors. It inhibits leukocyte trafficking, regulates the adhesion molecule expression and inhibits matrix metalloproteinase activity. The mechanism of action of IFN-β is complex and multifactorial but has been shown to reduce the biological activity of RRMS in several clinical class I trials [5].

The identification of peripheral markers that could reflect the clinical course of MS and the efficacy of treatment is a stimulating field of research and debate. An ideal biomarker is characterized by high sensitivity and specificity as well as a simple, cost effective, reproducible, and non-invasive detection method [6]. For instance, there are reports focusing molecules and autoantibodies as potential biomarkers in the MS disease course. Our focus in this chapter is on circulating leucocytes that can be considered during the follow of RRMS patients in remission *versus* relapse phase.
