Activation of histamine H2 receptors ameliorates experimental allergic encephalomyelitis.
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 H(2) receptor activation suppresses production of O(2)*-, TNF-alpha, and IL-12 by inflammatory cells, we tested the hypothesis that dimaprit, an H(2) 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.
Emerson
Mitchell R
MR
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Orentas
Diana M
DM
Lynch
Sharon G
SG
LeVine
Steven M
SM
D000818:Animals; D017259:Dimaprit / Q000494:pharmacology / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011970:Receptors, Histamine H2 / Q000378:metabolism*
D011970:Receptors, Histamine H2; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D017259:Dimaprit