Fig. 5

Regulation of macrophage activation and inflammation by spermine. In response to infection, injury, and other inflammatory stimuli, host macrophages produce various factors, such as TNF, IL-1, and NO, that are critical for an effective immune and inflammatory response but can also be harmful or even lethal to the host at high levels. In response to inflammatory stimuli, the activity of the spermine uptake system in activated macrophages is increased, leading to the incorporation of spermine from the surrounding environment. Spermine accumulation at inflammatory sites enhances intracellular macrophage uptake of spermine, resulting in the down-regulation of macrophage activation and inflammation.