Chemokines and chemokine receptors in the pathogenesis of multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic inflammatory and autoimmune, demyelinating disease of the central nervous system (CNS). Migration of autoreactive T lymphocytes into the CNS is one of the key processes that characterize the pathogenesis of MS and lead to the formation of inflammatory demyelinating CNS lesions. Chemokines represent a family of cytokines. They are low molecular weight soluble proteins, which affect target cells by binding to membrane chemokine receptors. Previous studies on experimental model of MS and experimental clinical studies confirmed that numerous chemokines and chemokine receptors, synthesized by CNS cells and various leukocyte populations, are an important component in the pathogenesis of MS. The essential role of chemokines in MS pathogenesis is to stimulate the migration of peripheral leukocytes into the CNS. In clinical pharmacological studies, it was demonstrated that the impact on expression of chemokines and chemokine receptors represents one of the mechanisms of action of pharmacological immunomodulatory agents used in the treatment of MS. It is difficult to allocate a pharmacological agent that permanently effectively suppresses the disease, and one of the reasons for that is complexity of the network of chemokines and chemokine receptors, in terms of their multitude and their variety of functions. Improved therapeutics that would be produced in the future, by acting through the individual components of complex network of chemokines and chemokine receptors, would selectively influence the migratory properties of pathogenic leukocyte populations, without compromising the functions of other components of the immune system.