Inhibitory effect of interferon-gamma on LPS-induced interleukin 1 beta production by isolated adult rat brain microglia.
The effect of interferon-gamma (IFN-gamma) on lipopolysaccharide (LPS)-induced cytokine production has been examined in adult rat brain microglia. Following treatment of isolated cells in vitro with LPS, interleukin-1 (IL-1) and interleukin-6 (IL-6) levels in culture supernatants, determined by bioassay, were increased in a dose-dependent manner. IL-6 was particularly sensitive to LPS-stimulation. Using in situ hybridisation techniques, the induction by LPS of IL-1 and IL-6 mRNA in cultured microglia has been demonstrated. When IFN-gamma was included, LPS-induced production of both IL-1 and IL-6 by microglia was significantly reduced and this effect was particularly marked in the case of IL-1. Comparisons with peritoneal macrophages demonstrate that whilst both cell types produce IL-1 and IL-6 in response to LPS, IFN-gamma had no significant effect on this response in peritoneal macrophages. This suggests potential control mechanisms which may be effective in down-regulating cytokine production by microglia in vivo.
Loughlin
A J
AJ
Multiple Sclerosis Laboratory, Institute of Neurology, London, U.K.
Woodroofe
M N
MN
D000818:Animals; D002478:Cells, Cultured; D004731:Endotoxins / Q000494:pharmacology; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C044101:endotoxin, Escherichia coli; D007371:Interferon-gamma