The Neuroimmunology of Tumour Necrosis Factor-α

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Tumour necrosis factor-α (TNFα) is a pleiotropic cytokine involved in the pathogenesis of a number of systemic diseases. Its involvement in neuroimmunology has recently been highlighted.

TNFα is produced in the central nervous system (CNS) by neurons, astrocytes and microglia. It possesses a diverse repertoire of activities within the CNS, ranging from facilitation of antigen presentation by astrocytes to direct toxicity on oligodendrocytes and myelin. Recent studies have found that TNFα may be important in the pathogenesis of bacterial meningitis, cerebral malaria, demyelinating diseases, acquired immunodeficiency syndrome (AIDS) and gliomas. Novel treatment methods are under active investigation, including inhibition of TNFα biosynthesis by agents such as dexamethasone, and the neutralisation of its biological effects with monoclonal antibodies or other experimental drugs.

Since CNS injury may be caused by an overabundant inflammatory response, the blunting of the activity of TNFα, a pivotal mediator in the cytokine cascade, may prove beneficial to the host. Any clinical role for TNFα will be defined by the balance between its beneficial and injurious effects. For instance, a therapeutic role for TNFα in gliomas will be based on the potential to minimise its effects while simultaneously increasing its tumour cytotoxicity.

Better understanding of the interactions of TNFα within the neuroimmunological cytokine network will lead to new treatments for disabling neurological diseases.

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