2-Buten-4-olide (2-B4O) inhibits experimental allergic encephalomyelitis (EAE) in Lewis rats.
Starvation is well known to induce immune suppression. Moreover, the concentration of 2-B4O, an endogenous sugar acid, is elevated in the circulation during starvation. To determine if these events are related, the influence of 2-B4O on experimental allergic encephalomyelitis (EAE) in Lewis rats, a model of human multiple sclerosis (MS), was studied. EAE, characterized by paralysis of hind legs, was induced by immunization with residues 68 to 84 (MB 68-84) of the guinea pig myelin basic protein (MBP) in complete adjuvant H37Ra. Interestingly, the daily administration of 2-B4O intraperitoneally from the day of MB 68-84 immunization (day 0) to day 20 dramatically suppressed the clinical severity of EAE. The daily administration of 2-B4O intraperitoneally from day 0 to day 7 also markedly reduced the clinical symptoms of EAE. In fact, passively induced EAE, using Con A activated spleen cells from rats immunized with MB 68-84 in H37Ra, was also inhibited by daily administration of 2-B4O. Histological examination confirmed clinical findings and revealed that mononuclear cell infiltration into the central nervous system was significantly inhibited by 2-B4O. To clarify the mechanism(s) responsible for suppression of EAE, the effects of 2-B4O on the immune responses to MB 68-84 were examined. When rats were treated daily 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 significantly reduced in 2-B4O treated rats as compared with saline treated rats. The proliferative response to MB 68-84 of spleen cells from 2-B4O treated rats was also significantly lower than that of saline treated rats. Our data demonstrate that 2-B4O has the potential to suppress autoimmune responses in both inductive and effector phases. 2-B4O may have significant potential to treat autoimmune diseases.
Naiki
M
M
Department of Hematology and Immunology, Nippon Zoki Pharmaceutical Co Ltd, Hyogo, Japan.
Takeoka
Y
Y
Yago
H
H
Kurimoto
Y
Y
Gershwin
M E
ME
Suehiro
S
S
D015107:4-Butyrolactone / Q000031:analogs & derivatives; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D005260:Female; D005663:Furans / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D004676:Myelin Basic Protein / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology
D005663:Furans; D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C079716:myelin basic protein 68-88; C004511:butenolide; D015107:4-Butyrolactone