PERIPHERAL LIPOPOLYSACCHARIDE STIMULATION INDUCES INTERLEUKIN-1-BETA MESSENGER-RNA IN RAT-BRAIN MICROGLIAL CELLS

The inflammatory cytokine interleukin-1 acts as an endogenous pyrogen in organisms affected by infectious diseases and has been shown to influence the activity of the central nervous system. Using in situ hybridization histochemistry, we have examined the cellular source of interleukin-1 beta in rat brain after peripheral stimulation with the bacterial lipopolysaccharide, a potent inducer of interleukin-1. Whereas no interleukin-1 beta messenger RNA could be detected in brains in unstimulated rats, lipopolysaccharide induced a transient, high and widespread expression of interleukin-1 beta messenger RNA in the entire brain. The highest levels of interleukin-1 beta messenger RNA were observed 6-8 h after stimulation with lipopolysaccharide. Using a combination of non-radioactive in situ hybridization and immunocytochemistry with the microglial-specific antibody OX-42, interleukin-1 beta messenger RNA-positive cells could be identified as microglia. We conclude that brain microglial cells are the major source of interleukin-1 beta messenger RNA after peripheral administration of lipopolysaccharide.