MICROGLIA DIGEST STAPHYLOCOCCUS-AUREUS INTO LOW-MOLECULAR-WEIGHT BIOLOGICALLY-ACTIVE COMPOUNDS

Excess sleep and fever are central nervous system (CNS) facets of the acute phase response; these responses are induced by microbial product s, such as muramyl peptides, via their ability to enhance cytokine pro duction. Although peripheral macrophages are known to digest bacteria, thereby releasing muramyl peptides that, in turn, stimulate cytokine production, it was unknown whether CNS phagocytes such as microglia al so had this capacity. Primary cultures of microglia were allowed to ph agocytize and digest Staphylococcus aureus radiolabeled with a cell wa ll-specific marker. Radiolabeled low molecular weight substances relea sed into the culture medium were partially purified and tested for the ability to induce excess sleep, fever, and cytokine production. These substances increased non-rapid eye movement sleep, electroencephalogr aphic slow-wave activity, and brain temperature after intracerebrovent ricular injection into rabbits. They also induced interleukin-1, tumor necrosis factor, and the interleukin-1 receptor antagonist production in human monocytes. Results suggest that microglia perform fundamenta l macrophage functions and further implicate microglia as resident imm unocompetent cells.