Atypical inflammation in the central nervous system in prion disease

The inflammatory response in prion diseases is dominated by microglial activation. Contrary to their profile in vitro none of the pro-inflammatory cytokines interleukin-1beta, interleukin-6, or tumour necrosis factor-alpha are significantly upregulated in the ME7 model of prion disease. However, two major inflammatory mediators are elevated: transforming growth factor-beta1 and prostaglandin E2. This cytokine profile is the same as that reported for macrophages during phagocytosis of apoptotic cells and indeed transforming growth factor-beta1 and prostaglandin E2 are responsible for the downregulated phenotype of these macrophages. Transforming growth factor-beta1 may also have roles in extracellular matrix deposition and in amyloidogenesis and may play a direct role in disease pathogenesis. There is also now evidence to suggest that a peripheral infection, and its consequent systemic cytokine expression, may drive central nervous system cytokine expression and perhaps exacerbate disease.