Cyclosporin A treatment of an induced attack in a chronic relapsing model of experimental allergic encephalomyelitis

Abstract

Chronic relapsing experimental allergic encephalomyelitis (EAE) was induced in 8-week-old SJL/J mice by injecting an encephalitogenic emulsion on Day 0 and Day 7. A third injection was given on Day 70 postinoculation (PI) which precipitated an attack with high mortality (62%) after 7–9 days. Cyclosporin A (CsA) was given at doses of 5, 2, and 0.5 mg per mouse, one or three times per week starting from Day 40 PI and continuing over the next 17 days. High serum levels of CsA were measured by radioimmunoassay. However, gross and microscopic pathological examination showed no indication of hepatic or renal toxicity at these doses. In the CsA-treated mice, there was a dose-dependent shortening of the length and severity of the attack forced by challenge with the third injection. The mortality was significantly ( P < 0.05) reduced when compared with the non-CsA-treated controls. In addition, the data demonstrate a decrease of lymphocyte-derived chemotactic factor produced from phytohemagglutinin-stimulated spleen cells of mice with chronic relapsing EAE treated with CsA when compared to normal mice and mice with chronic relapsing EAE treated with vehicle alone. We conclude that it is possible to effect an induced acute attack in ongoing chronic relapsing EAE with CsA treatment.