Histamine and histamine receptors in pathogenesis and treatment of multiple sclerosis

Neuropharmacology. 2010 Sep;59(3):180-9. doi: 10.1016/j.neuropharm.2010.05.005. Epub 2010 May 21.

Abstract

Multiple sclerosis (MS) is an autoimmune disease associated with chronic inflammatory demyelination of the central nervous system (CNS). Due to disease complexity and heterogeneity, its pathogenesis remains unknown and despite extensive studies, specific effective treatments have not yet been developed. The factors behind the initiation of the inflammatory reactions in CNS have not been identified until now. MS is considered as a complex disease depending on genetic as well as environmental factors. Experimental autoimmune encephalomyelitis (EAE) is the preferential experimental rodent model for MS. Histamine [2-(4-imidazole) ethylamine] is a ubiquitous inflammatory mediator of diverse physiological processes including neurotransmission, secretion of pituitary hormones, and regulation of the gastrointestinal and circulatory systems which can modulate immune responses. Histamine functions are mediated through four G-protein coupled receptors that are named H1-H4 receptor. Histamine is implicated as an important factor in pathophysiology of MS and EAE. It has been shown that histamine can change the permeability of blood brain barrier, which leads to elevation of infiltrated cells in CNS and neuroinflammation. In contrast, there are evidence that show the protective role of histamine in MS and its animal model, EAE. In this review, we try to clarify the role of histamine in pathogenesis of MS, as well as we evaluate the efficacy of histamine receptors agonists and antagonists in treatment of this disease.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Histamine / metabolism*
  • Histamine / therapeutic use
  • Histamine Agents / therapeutic use*
  • Humans
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / physiopathology
  • Receptors, Histamine / classification
  • Receptors, Histamine / physiology*

Substances

  • Histamine Agents
  • Receptors, Histamine
  • Histamine