The immune system and scrapie pharmacological strategies for control

A functional immune system is required for efficient experimental transmission of scrapie and for TSE agents to cross the 'species barrier'. Outram and Dickinson have shown that immunologically immature, perinatal mice are less susceptible to scrapie infection than their 3-week-old littermates, and SCID mice are relatively refractory to infection by peripheral, natural, routes of infection. Various immuno-modulators can affect the incubation period of peripherally-routed scrapie if administered at the time of infection. Phytohemagglutinin and methanol-ex-tracted BCG increase susceptibility to infection, while prednisone acetate, dexamethazone, arachis oil and the antiviral agent HPA-23 have the opposite effect. However, interferon, antilymphocyte serum, cyclophosphamide, neonatal thymectomy or whole body irradiation fail to alter incubation period. The polyanions, dextran sulfate and pentosan polysulf-ate, increase survival time considerably, even when administered weeks after peripheral infection, and can completely protect against disease in some cases. They reduce the effective titer of infectivitv and inhibit PrPSc accumulation, most probably by removing PrP1 from the cell surface by stimulating endo-cytosis, and are therefore of potential therapeutic value. Amphotericin B, a polyene antibiotic, is unique in delaying scrapie replication and PrPs" accumulation in some models infected by an intracerebral route. It is, however, highly toxic and has to be administered daily throughout pathogenesis. Safer derivatives are being developed.

See also: Neurological infections; Ovine immune system.

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