Neuroreport 2002 Aug 7;13(11):1407-10
Emerson MR, Orentas DM, Lynch SG, LeVine SM.
Department of Molecular and Integrative Physiology; 1Department of Neurology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160; 2Maxim Pharmaceutical Company, San Diego, CA, USA.
Experimental allergic encephalomyelitis (EAE), a model of multiple sclerosis, is an autoimmune, demyelinating disease of the CNS.
Pro-inflammatory cytokines (e.g. tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12) and reactive oxygen species are implicated in promoting EAE.
Since histamine H2 receptor activation suppresses production of O2.-, TNF-alpha, and IL-12 by inflammatory cells, we tested the hypothesis that dimaprit, an H2 agonist, would reduce the clinical severity and pathology of EAE.
Dimaprit treatment significantly reduced clinical signs compared to vehicle in both C57BL/6 and iNOS deficient EAE mice.
Furthermore, dimaprit significantly reduced CNS staining for lectin-positive macrophages and decreased extravasated albumin staining, an indicator of blood-brain barrier leakage.
These data provide a rationale for exploring H2 receptor activation for therapeutic value in multiple sclerosis.