Cytokine regulation of neuronal survival.
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-1 alpha, 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-1 alpha, and to a lesser extent by interleukin-1 beta. Exogenous interleukin-1 alpha 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.
Brenneman
D E
DE
Unit on Neurochemistry, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Schultzberg
M
M
Bartfai
T
T
Gozes
I
I
D000818:Animals; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000502:physiology*; D007106:Immune Sera / Q000276:immunology / Q000502:physiology; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D016207:Cytokines; D007106:Immune Sera; D007375:Interleukin-1; D014660:Vasoactive Intestinal Peptide