Immunocytochemical appearance of cytokines, prostaglandin E-2 and lipocortin-1 in the CNS during the incubation period of murine scrapie correlates with progressive PrP accumulations

The appearance of immunoreactive interleukin (IL)-1 beta, IL-6 and tumour necrosis factor (TNF)-alpha, prostaglandin (PG) E-2 and lipocortin-l in the central nervous system was investigated during the development of lesions in a 301V/VM murine scrapie model. Focal PrPSc deposition was present after 30 days of the 115-120 day incubation period; this immunoreactivity increased in intensity and distribution thereafter. Staining for IL-1 beta and TNF alpha. in perivascular macrophages, and PGE(2) immunoreactivity in astrocytes, was detected in those areas showing PrPSc deposition from 60 days. Increased GFAP and F4/80 immunoreactivity, indicating activation of astrocytes and microglia, was also evident in these areas from 60 days. Glial cytokine and lipocortin immunoreactivity was detected after 90 days, in the absence of clinical signs, The disease-induced cytokine, PG and lipocortin immunoreactivity occurred only in those brain areas showing PrPSc deposition, glial activation and, in later stages, vacuolation. These findings support the concept that PrPSc deposition induces glial cytokine production. These glial cytokines may contribute to the development of the pathological lesions in scrapie. (C) 1997 Elsevier Science B.V.