2-BUTEN-4-OLIDE (2-B4O) INHIBITS EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS (EAE) IN LEWIS RATS

Starvation is well known to induce immune suppression. Moreover, the c oncentration of 2-B4O, an endogenous sugar acid, is elevated in the ci rculation during starvation. To determine if these events are related, the influence of 2-B4O on experimental allergic encephalomyelitis (EA E) in Lewis rats, a model of human multiple sclerosis (MS), was studie d. EAE, characterized by paralysis of hind legs, was induced by immuni zation with residues 68 to 84 (MB 68-84) of the guinea pig myelin basi c protein (MBP) in complete adjuvant H37Ra. Interestingly, the daily a dministration of 2-B4O intraperitoneally from the day of MB 68-84 immu nization (day 0) to day 20 dramatically suppressed the clinical severi ty of EAE, The daily administration of 2-B4O intraperitoneally from da y 0 to day 7 also markedly reduced the clinical symptoms of EAE. In fa ct, passively induced EAE, using Con A activated spleen cells from rat s immunized with MB 68-84 in H37Ra, was also inhibited by daily admini stration of 2-B4O. Histological examination confirmed clinical finding s and revealed that mononuclear cell infiltration into the central ner vous system was significantly inhibited by 2-B4O. To clarify the mecha nism(s) responsible for suppression of EAE, the effects of 2-B4O on th e immune responses to MB 68-84 were examined. When rats were treated d aily with 2-B4O for 15 days after immunization with MB 68-84 in H37Ra, the delayed-type hypersensitivity (DTH) response to MB 68-84 was sign ificantly reduced in 2-B4O treated rats as compared with saline treate d rats. The proliferative response to MB 68-84 of spleen cells from 2- B4O treated rats was also significantly lower than that of saline trea ted rats. Our data demonstrate that 2-B4O has the potential to suppres s autoimmune responses in both inductive and effector phases. 2-B4O ma y have significant potential to treat autoimmune diseases. (C) 1995 Ac ademic Press Limited