Hydroxyzine inhibits experimental allergic encephalomyelitis (EAE) and associated brain mast cell activation

Experimental allergic encephalomyelitis (EAE) has been used as an animal mo del for the human demyelinating disease multiple sclerosis (MS). In acute M S or EAE, early disruption in the integrity of the blood-brain-barrier (BBB ) precedes brain infiltration by inflammatory cells or any clinical evidenc e of disease. BBB permeability could be affected by vasoactive mediators an d cytokines released from perivascular brain mast cells. We investigated th e number and degree of activation of brain mast cells in EAE and the effect of the heterocyclic histamine-1 receptor antagonist hydroxyzine, a piperaz ine compound known to also block mast cells. Acute EAE was induced in Lewis rats by immunization with whole guinea pig spinal cord homogenate and comp lete Freund's adjuvant (CFA). A second group of animals were treated orally with hydroxyzine for one day before immunization and then continuously for 14 days. Control rats were treated with CFA or hydroxyzine alone. The clin ical progression of EAE was assessed on days 10, 12 and 14 after immunizati on. The number of metachromatic mast cells and the degree of degranulation was assessed in the thalamus with light microscopy. At day 14, there was a three-fold increase in the number of brain mast cells with EAE, as compared to controls. These cells were positive for the immunoglobulin E binding pr otein (Fc epsilon RI), while those from control rats were not. Over 40% of all thalamic mast cells studied in EAE showed partial staining or extruded secretory granule indicative of secretion. Hydroxyzine treatment inhibited (p < 0.05) the progression and severity of EAE by 50% and the extent of mas t cell degranulation by 70% (p < 0.05). These findings indicate that brain mast cells are associated with EAE development and that inhibition of their activation correlates positively with the clinical outcome. (C) 2000 Inter national Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved.