Abstract
Multiple sclerosis (MS) is a chronic inflammatory, neurodegenerative disease of the CNS whose pathogenesis remains largely unknown, and available therapies are rarely successful in reversing neurological deficits or stopping disease progression. Ongoing studies on MS and the widely used murine model of experimental autoimmune encephalomyelitis (EAE) are focused on the many components of this complex and heterogeneous neurodegenerative disease in the hope of providing a mechanism-based characterization of MS that will afford successful strategies to limit and repair the neuronal damage. Recently, histamine has been postulated to have a key regulatory role in EAE and MS pathogenesis. Histamine is a mediator of inflammation and immune responses, exerting its many actions through four G protein-coupled receptors (H1,2,3,4R) that signal through distinct intracellular pathways and have different therapeutic potentials as they vary in expression, isoform distribution, signaling properties, and function. Immune cells involved in MS/EAE, including dendritic cells (DCs) and T lymphocytes, express H1R, H2R and H4R, and histamine may have varying and counteracting effects on a particular cell type, depending on the receptor subtypes being activated. Here, we review evidence of the complex and controversial role of histamine in the pathogenesis of MS and EAE and evaluate the therapeutic potential of histaminergic ligands in the treatment of autoimmune diseases.
Highlights
MS: A COMMON INFLAMMATORY-DEGENERATIVE central nervous system (CNS) DISEASE Multiple sclerosis (MS) is the most common, non-traumatic cause of neurological disability among young adults in Western Europe and North America
Histamine is a mediator of inflammation and immune responses, exerting its many actions through four G protein-coupled receptors (H1,2,3,4R) that signal through distinct intracellular pathways and have different therapeutic potentials as they vary in expression, isoform distribution, signaling properties, and function
MS is characterized by inflammation of the central nervous system (CNS) in which focal lymphocytic infiltrations lead to damage of myelin and axons associated with neurological
Summary
Histamine and neuroinflammation: insights from murine experimental autoimmune encephalomyelitis. We review evidence of the complex and controversial role of histamine in the pathogenesis of MS and EAE and evaluate the therapeutic potential of histaminergic ligands in the treatment of autoimmune diseases. As with other autoimmune diseases, MS shows moderate polygenic inheritability and may be caused or exacerbated by environmental exposure such as viral infections or vitamin D deficiency (Correale et al, 2009) It is characterized by clinical and genetic heterogeneity and with individuals with MHC class II complex genes being most susceptible (Ballerini et al, 2004; Gourraud et al, 2011). Possible explanations of the therapeutic potential of H1R antagonists come from preclinical results in experimental allergic encephalomyelitis (EAE) in mice
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