The importance of Cytokines

Cytokines are proteins that regulate the immune system and that participate in intercellular communications. A complex cytokine network is involved in normal immune function, and this network is comprised of positive and negative feedback loops that enhance or suppress the response. Many immune-mediated diseases (e.g rheumatoid arthritis, multiple sclerosis) involve dysregulated cytokines and other inflammatory molecules. This can be manifested either by defective production of suppressive factors or by overproduction of  pro-inflammatory cytokines and other molecules.

Cytokine imbalance in MS

Studies have shown that MS patients have a much higher number of neuro-antigen, e.g. myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) auto-reactive T-cells, which are in an increased state of activation compared with healthy controls, and which increase during exacerbation (relapse).

Cytokines from activated T cells and macrophages have been strongly implicated in the pathogenesis of MS. For example, the up-regulation of adhesion molecules on endothelial cells and the subsequent infiltration of activated T cells into the CNS are immunopathogenic events controlled by pro-inflammatory cytokines such as tumour necrosis factor-ɑ (TNF-ɑ), interleukin-1β (IL-1β) and interferon-ɣ (IFN-ɣ). Furthermore studies have shown that these cytokines exert direct myelinotoxic properties and prolong the disease process in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. TNF-ɑ, IL-1β and IFN-ɣ have all been shown to be present in CNS active lesions in MS and elevated amounts of these cytokines are secreted from MS peripheral blood mononuclear cells (PBMC). Many studies have also shown that an increase in these inflammatory cytokines coincides with the relapse phase of the disease. Furthermore some studies have shown that transforming growth factor-beta1 (TGF-β1), a potent anti-inflammatory and immunosuppressive cytokine is reduced during the relapse phase and increases as the patient enters remission. The balance between biologically active TGF-β1 and the pro-inflammatory TNF-ɑ, IL-1β and IFN-ɣ is dysregulated during MS relapse-remission. The actual processes of axonal damage e.g. chronic inflammation, demyelination and astrogliosis in MS is complex but white matter inflammation and demyelination are considered to determine disease severity, whilst recent studies suggest that axonal damage in MS begins in the early stages of the disease and contributes to disability. Furthermore some have considered metabolic disturbances in some MS patients to be behind primary oligodendrocyte damage with secondary autoimmune-demyelination.