Inhibition of chronic relapsing experimental allergic encephalomyelitis in the mouse by the alkyl-lysophospholipid ET-18-OCH3.
The effect of the anti-tumour agent alkyl-lysophospholipid (ALP) ET-18-OCH3 on the development of chronic relapsing experimental allergic encephalomyelitis (CREAE) in the mouse was investigated. Experimental allergic encephalomyelitis developed in the majority (greater than 96%) of mice immunized with autologous spinal cord homogenate in Freund's complete adjuvant. Alkyl-lysophospholipid, in doses of 25 mg/kg/day or 50 mg/kg/day, inhibited the onset of clinical signs of acute phase CREAE when orally administered starting on the day of disease induction. Similarly if treatment with 50 mg/kg/day was delayed until day 9 post-inoculation the incidence of disease and severity of clinical signs were also significantly reduced (P less than 0.02) as compared with vehicle fed animals. However, when treatment began on day 12, just prior to the onset of clinical disease, although the incidence of disease was not significantly altered the severity of disease was significantly (P less than 0.002) reduced compared with vehicle treated animals. These data suggest that although the major effect of ALP is on the inhibition of the generation of the autoimmune response there appeared to be some therapeutic benefit at a later stage of acute disease. Therefore, this study was extended to the treatment of post-acute phase remission animals. It was found that the oral administration of 50 mg/kg/day marginally reduced and that 75 mg/kg/day significantly (P less than 0.05) reduced the incidence of relapsing disease compared with vehicle treated controls. This suggests that ET-18-OCH3 may have some potential in the treatment of ongoing autoimmune disease of the central nervous system.
Baker
D
D
Department of Pathology, Royal College of Surgeons, London, U.K.
O'Neill
J K
JK
Amor
S
S
Khamashta
M A
MA
Turk
J L
JL
D000818:Animals; D002908:Chronic Disease; D004341:Drug Evaluation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010742:Phospholipid Ethers / Q000627:therapeutic use*
D010742:Phospholipid Ethers; C026659:edelfosine