**2. Multiple sclerosis**

MS is an autoimmune disease of the brain and the spinal cord characterized by chronic inflammation, demyelination, gliosis and neuronal loss. The demyelination consists of the damage of the myelin sheath surrounding nerves, consequently affects the function of the nerves. The pathological hallmark of chronic MS is the demyelinated plaque or lesions, which consists of a well-demarcated hypocellular area characterized by the loss of myelin sheaths or oligodendrocytes, relative preservation of axons, and the formation of astrocytic scars [1].

The etiology of MS remains elusive, with a complex multifactorial system implicated, in which environmental factors are hypothesized as interacting with genetically susceptible individuals. MS causes a heterogeneous array of symptoms and signs because of the differential involvement of motor, sensory, visual and autonomic systems with serious physical disability in young adults, especially women [2, 4, 7].

The CNS is frequently described as an immune-privileged site, evidence supports the notion that the CNS receives limited immune surveillance by peripheral lymphocytes under physiological conditions. New findings provide a mechanism by which large particles and immune cells can drain from the brain and interface directly with the peripheral immune system [8, 9].

MS is triggered in the periphery or in the CNS. The CNS-extrinsic (peripheral) model is the most widely accepted and is consistent with the method used to induce experimental autoimmune encephalomyelitis (EAE), the animal model for neuroinflammation. The autoreactive T cells from MS patients may become activated in the periphery as a result of a molecular mimicry, gain access to the CNS, and T cells generated against non-self-epitopes (viral or microbial antigens) cross-react with self-myelin epitopes of similar sequence [10–12].

85% of patients present a RR form of MS, characterized by discrete episodes of neurological dysfunction (relapses) separated by clinical stable periods with lack of disease progression (remissions). More than 30% remain in the RRMS form of the disease into old age [7, 11–13].

Relapse is the clinical result of an acute inflammatory focal lesion and is typically discernible using magnetic resonance imaging. Relapse is defined as newly appearing neurological symptoms in the absence of fever or infections that last for more than 24 hours and are separated from the previous event by at least one month. The frequency of relapses can vary widely among patients as well as during different periods during an individual patient's disease. The relapse tends to be present for a limited time – days or weeks – and can lead to full recovery or can leave sequelae.

*Peripheral Biomarkers in Multiple Sclerosis Patients Treated with Interferon-Beta DOI: http://dx.doi.org/10.5772/intechopen.99006*

At present time, no clinical features or biomarkers that are predictive of relapse rates have been identified. The signs and symptoms that occur during relapses are also diverse and unpredictable [3, 8, 11].

Immunological characteristics of MS lesions have been reflected in circulating immune cells of MS patients. Peripheral blood provides a 'window' into the immunopathogenesis of MS. The immunological disturbances that underlie MS can be observed not only in the CNS, but also through examination of peripheral immune cells [14].

### **3. Therapeutic management**

IFN-β and glatiramer acetate have been used as first-line disease-modifying therapy for RRMS. More than two decades have passed since IFN-β was found to be effective in the management of MS. IFN-β treatment efficacy has been shown by a decrease in the annual relapse rate, in disability progression and in inflammatory brain lesions, resulting in the approval of different IFN-β preparations [15–17].

IFNs are naturally occurring cytokines, secreted by various cells such as fibroblasts, NK cells, leukocytes, and epithelial cells in response to pathogens such as bacteria, viruses, parasites, and tumor cells, as well as other foreign substances. They have a wide range in anti-inflammatory processes, regulation of cell growth and modulation of immune responses [18, 19].

IFN-β binds to the interferon receptor, activates the Janus kinase/signal transducer and the activator of transcription (STAT) pathway to phosphorylate STAT1 and STAT2. The activation of interferon-stimulated genes leads to the production of antiviral, antiproliferative, and antitumour products. The effectiveness of IFN-β in the treatment of MS may rely on both anti-viral and immunomodulatory aspects [20, 21].

IFN-β was the first immunomodulatory therapy approved by the U.S. Food and Drug Administration and is the most widely prescribed treatment for MS; it is generally well tolerated and overall reduces the relapse rate by 30% in patients with RRMS [4].

Several IFN-β preparations have been approved with differing structures (glycosylated IFN-β-1a vs. non-glycosylated IFN-β-1b), formulation (lyophilized vs. liquid), used excipients (e.g., containing serum albumin or not), modification (pegylation), dosage (protein load and bioactivity), route of administration (subcutaneous vs. intramuscular), or frequency of injection (ranging from bi-weekly to every other day). IFN-β shows high tissue distribution; however, it is not supposed to cross the BBB and exerts its immunomodulatory mechanism in the peripheral compartment. IFN-β is cleared via renal and hepatic pathways, in which catabolism seems to be important rather than simple excretion [15].

The therapeutic benefit of IFN-β in MS has been proven in several large clinical trials, with the effect of IFN-β therapy being more studied on T and B cells [22]. In spite of this, it is known that the biological functions of IFN-β act in both innate and adaptive immune responses and may influence phenotype and functions of all MS-relevant immune cells [23].
