Chemokines and chemokine receptors: potential therapeutic targets in multiple sclerosis.
Multiple sclerosis (MS) is a common inflammatory and demyelinating disease of the central nervous system (CNS), which causes progressive neurological disability. The disease is characterised pathologically by destruction of the myelin sheaths, which surround nerve fibres in the CNS. It is believed that this tissue damage in the brain and spinal cord of MS patients is caused by an inflammatory response that is initiated when autoreactive T cells, specific for myelin antigens, cross the blood-brain barrier and detect their antigen within the CNS. As a result, most therapies to date have been immunosuppressive and/or anti-inflammatory in nature, targeting the processes involved in activation and migration of leukocytes and promotion of the immune response. Over the last decade, a family of chemotactic cytokines called chemokines, have been found to be involved in the trafficking of leukocytes in both the normal and pathological states. The expression of these chemokines and their receptors is increased during the acute phase of MS and also in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). As a result, these chemokines have become an emerging focus for research into novel therapeutics for EAE and ultimately MS. This review will briefly describe the structure and function of chemokines and their receptors, before discussing the latest advances in developing pharmacological agents to block the effects of chemokines involved in promoting the inflammatory response in EAE and MS.
Muller
Diane M
DM
Neuroimmunology Research Centre, The University of Queensland, C Floor, Clinical Sciences Building, Royal Brisbane Hospital, Herston, Australia 4029. diane.muller@uq.edu.au
Pender
Michael P
MP
Greer
Judith M
JM
D000818:Animals; D018925:Chemokines / Q000276:immunology*; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000378:metabolism
D018925:Chemokines; D019707:Receptors, Chemokine