Interleukin (IL)-1beta-mediated apoptosis of human astrocytes

Apoptosis of brain cells is observed in many inflammatory disorders of the central nervous system. Nitric oxide (NO) has been shown to induce apoptosis in several brain cell types, but not previously in astrocytes. In the present study, the hypothesis was examined that interleukin (IL)-1beta would induce production of NO by astrocytes which, in turn, would signal apoptotic death in these glial cells. TUNEL staining demonstrated apoptosis in astrocytes treated with IL-1beta. Using an ELISA method, IL-1 receptor antagonist protein completely abrogated this astrocyte apoptosis, while N(G)monomethyl-L-arginine partially prevented apoptosis but almost entirely blocked NO production. Thus, IL-1beta appears to signal apoptosis of astrocytes by a mechanism involving, in part, the induction of NO.