CEREBROSPINAL-FLUID

Examination of cerebrospinal fluid (CSF) in the context of multiple sclerosis (MS), is valuable for several reasons. First, routine diagnostic evaluation of CSF cell counts and various forms of immunoglobulin determination are important to differentiate MS from other diseases. Second, because MS most probably is an organ-specific inflammatory disease and CSF is often the closest one can get to the target organ, examination of this fluid may allow basic studies on the immunopathogenesis of the disease, and indications of different aspects of inflammation should be considered when evaluating treatments aimed at reducing central nervous system inflammation. This article describes measurements taken at the cellular level in blood and CSF, of myelin-antigen autoreactive B- and T-cell responses, as well as cytokine production. Patients with MS display greatly increased numbers of cells in the CSF that produce antibodies against a variety of myelin antigens, such as myelin basic protein, proteolipid protein, and myelin-oligodendrocyte glycoprotein. Such antibodies may promote demyelination, and autoreactive B cells may enhance antigen presentation to T cells. There is also an increased number of T cells in MS, which in response to a broad range of myelin antigens and peptides, produce cytokines. The production of interferon-gamma, belonging to the T helper-1 type of cells, may have a disease up-regulatory role, while production of other cytokines, such as transforming growth factor beta, may counteract disease. Accurate measurements of cellular production of cytokines will be important in the design and monitoring of immunotherapy.