Lipopolysaccharide and IL-1 alpha activate CNS pathways as measured by NK cell activity

The effect of lipopolysaccharide (LPS) on murine unstimulated and prestimulated natural killer (NK) cells and its ability to serve as an unconditioned stimulus was investigated. LPS injection induced a statistically significant increase in NK cell activity when compared with saline-treated control groups. To demonstrate the existence of communication between the peripheral immune system and the central nervous system (CNS), we used a single-trial conditioning paradigm in which camphor served as the conditioned stimulus (CS) and LPS as the unconditioned stimulus (US). Once a CS/US association is made, exposure of animals to the CS alone results in the conditioned response (i.e., increase in NK cell activity). Using 50 micrograms of LPS as the US produced a low but significant increase in NK cell activity when compared to control groups. However, 10 micrograms of LPS did not show a significant increase in NK cell activity. We also observed that interleukin-1 alpha (IL-1 alpha) injected intracisternally can serve as a US to condition a central neuroendocrine pathway. Because the dose of IL-1 alpha employed was too small to raise NK cell activity in the spleen, the NK cells themselves were formally not subjected to conditioning. These observations suggest that LPS and IL-1 alpha conditions the brain and that NK cell activity can be used as an indicator system to detect neuroendocrine signals arising from the activated pathway(s).