Interleukin-18 expression after focal ischemia of the rat brain: association with the late-stage inflammatory response.
Interleukin-18, previously designated interferon gamma-inducing factor, is a proinflammatory cytokine structurally related to interleukin-1beta and is therefore considered a member of the growing family of interleukin-1-like cytokines. Both interleukin-18 and -1beta are synthesized as inactive precursors that necessitate cleavage by caspase-1 for functional activity. In this study, the authors analyzed the expression pattern of interleukin-18, -1beta, and caspase-1 in focal brain ischemia induced in rats either by permanent middle cerebral artery occlusion or by photothrombosis of cortical microvessels. Using reverse transcriptase-polymerase chain reaction, they found a delayed increase of interleukin-18 mRNA starting at 48 hours and reaching its peak between 7 and 14 days after ischemia. In contrast, interleukin-1beta mRNA peaked within 16 hours and was downregulated thereafter. The time course of caspase-1 mRNA expression paralleled that of interleukin-18, but not of interleukin-1beta mRNA. Immunocytochemically, interleukin-18 expression was localized to ED1-positive phagocytic microglia/macrophages infiltrating the necrotic lesion between 3 and 6 days after ischemia. In contrast, interleukin-1beta immunoreactivity was expressed by ramified microglia in the infarct border zone and remote ipsilateral cortex during the first 16 hours postlesion. Induction of interleukin-18 was not accompanied by detectable expression of interferon-gamma mRNA. Their data show spatial and temporal diversity in interleukin-1 and -18 cytokine family expression in brain ischemia, and suggest a role of the interleukin-18/caspase-1 pathway in late-stage inflammatory responses to focal brain ischemia.
Jander
Sebastian
S
Department of Neurology, Heinrich-Heine University, Düsseldorf, Germany.
Schroeter
Michael
M
Stoll
Guido
G
D000818:Animals; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D013223:Statistics as Topic; D013997:Time Factors
D007375:Interleukin-1; D020382:Interleukin-18; D012333:RNA, Messenger; D007371:Interferon-gamma; D020170:Caspase 1