Potential link between interleukin-6 and arachidonic acid metabolism in Alzheimer's disease.
Prostaglandins (PGs) and cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6), have been implicated in the etiopathology of various inflammatory and degenerative disorders, including Alzheimer's disease (AD). Previously, we detected the presence of IL-6 in cortices of AD patients. On the other hand, non-steroidal antiinflammatory drugs (NSAIDs), potent inhibitors of prostaglandin synthesis, have been shown to be beneficial in the treatment of AD. Until now, it remained unclear whether and how these two observations were functionally connected. Here, we show that PGs are able to induce IL-6 synthesis in a human astrocytoma cell line. PGE1 and PGE2, but not PGD2 and PGF2 alpha, led to a rapid and transient induction of astrocytic IL-6 mRNA, followed by IL-6 protein synthesis. Furthermore, PGE2 potentiated IL-1 beta-induced IL-6 mRNA synthesis. These results suggest a possible link between the release of PGs from activated microglia and the astrocytic synthesis of IL-6, which itself may affect neuronal cells, as hypothesized for Alzheimer's disease. Finally we demonstrate that microglia are a strong source of PGE2 synthesis indicating that these cells may act as the origin of the pathogenic cascade.
Fiebich
B L
BL
Department of Psychiatry, University of Freiburg Medical School, Federal Republic of Germany.
Hüll
M
M
Lieb
K
K
Schumann
G
G
Berger
M
M
Bauer
J
J
D000527:Alprostadil / Q000494:pharmacology; D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism*; D001254:Astrocytoma; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017628:Microglia / Q000502:physiology*; D018448:Models, Immunological; D008959:Models, Neurological; D015230:Prostaglandin D2 / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D015850:Interleukin-6; D011453:Prostaglandins; D012333:RNA, Messenger; D016718:Arachidonic Acid; D015237:Dinoprost; D000527:Alprostadil; D015232:Dinoprostone; D015230:Prostaglandin D2