Radiation enhances tumor necrosis factor alpha production by murine brain cells

Astrocytes and microglial cells cultured from murine brain were stimulated to produce tumor necrosis factor alpha (TNF) by exposure to lipopolysaccharide (LPS). TNF alpha production began within 2 h with maximum production between 4 and 8 h after stimulation. Clinically relevant low (2 Gy), but not high (8 Gy), doses of radiation significantly increased TNF production by astrocytes and microglial cells in response to LPS. The radiation effect was even more marked with multiple 2 Gy doses. TNF is cytotoxic for oligodendrocytes and for certain tumor cells. It increases vascular permeability and enhances immune responses as well as having other biological effects. It is conceivable that production of TNF by astrocytes and microglial cells during clinical radiation therapy might influence the responses of tumor and/or normal CNS tissues.