Cytokine Regulation of Neuronal Survival

Abstract: Interleukin‐1 is a cytokine involved in the immune response to infection and inflammation as well as a growth promotor for several cell types. Interleukin‐1‐like immunoreactive material has been found in the nervous system. We now show that antisera, which blocked the T‐cell proliferative effects of interleukin‐1α, decreased neuronal cell counts (to 40% of control) in dissociated spinal cord cultures derived from fetal mice. This neuronal loss was prevented by addition of interleukin‐1α, and to a lesser extent by interleukin‐1β. Exogenous interleukin‐1α increased the survival of neurons when added to cultures in which the electrical activity was blocked with tetrodotoxin, whereas no such cytokine‐related increase in neuronal survival was observed in electrically active cultures. The antiserum‐induced death could also be prevented by cotreatment of the cultures with 0.1 nM vasoactive intestinal peptide, a substance that induces the secretion of neuronal trophic factors from nonneuronal spinal cord cells and thereby increases neuronal survival in electrically inactive cultures. These studies indicate that the cytokine interleukin‐1, or an immunologically cross‐reactive protein, can increase neuronal survival.