Suppression of Experimental Allergic Encephalomyelitis by 6-Hydroxyphthalaldehydic Acid, O-(p-Chlorobenzyl)Oxime (EN3638)

Abstract

EN3638 is a new oxime derivative of salicylic acid that has immunosuppressive properties. Oral administration of the compound to rats during the incubation period of experimental allergic encephalomyelitis (EAE) delayed the onset of clinical signs. EN3638 was effective in both ordinary and hyperacute forms of EAE. Doses of 50, 100, or 150 mg/kg daily, 250 mg/kg three times a week, or 400 mg/kg twice a week suppressed both clinical and histologic evidences of EAE during the course of therapy (as long as 4 weeks) and for 8 or more days thereafter. Clinical EAE developed after a full incubation period after discontinuance of EN3638, probably due to the persisting depot of antigen in oil. When EAE was produced without an oily depot, a single dose suppressed the disease for at least 5 weeks in some rats. EN3638 was effective when given only in the second half of the incubation period but not when given at the time that EAE lesions and signs develop. Passive transfer experiments suggested that the drug prevented and even reversed sensitization to neural antigens. It had only slight effect on fully sensitized lymphoid cells or on the recruitment of nonimmune inflammatory cells in the nervous system, and it was not acting as a source of salicylate or as an adrenocortical stimulator.