Gene expression of IL-10 in relationship to TNF-alpha, IL-1beta and IL-2 in the rat brain following middle cerebral artery occlusion.
To systematically elucidate the gene expression of inflammatory and immune modulators following middle cerebral artery occlusion (MCAO) in the rat, we studied interleukin-10 (IL-10) along with tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and interleukin-2 (IL-2). Gene expression of these cytokines was studied ipsilateral and contralateral to the MCAO, with mRNA expression levels evaluated 2, 4, 6, 8 and 12 h following permanent MCAO by reverse transcriptase polymerase chain reaction (RT-PCR). In the ischemic hemisphere TNF-alpha and IL-1beta mRNA increased at 2 h following MCAO and peaked at 6 h, with IL-10 mRNA detected only at 6 h. Contralaterally, both TNF-alpha and IL-1beta mRNAs were expressed with a similar pattern to that in the ischemic hemisphere, but at lower levels, with no contralateral IL-10 expression. There was no difference in IL-2 gene expression between control and experimental animals in either hemisphere. These results demonstrate that IL-10 and TNF-alpha, IL-1beta gene expression is induced early following MCAO. The temporal profile of these cytokines is similar to that seen in sepsis, where TNF-alpha induces IL-10; subsequently IL-10 inhibits TNF-alpha expression. The similarity of the temporal profile of cytokine expression in sepsis and cerebral ischemia suggests that IL-10 should be studied as a potential inhibitor of TNF-alpha production in ischemic brain tissue. The factors inducing contralateral expression of the inflammatory cytokines, TNF-alpha and IL-1beta, along with the potential clinical significance of this remote cytokine gene expression, merit further study.
Zhai
Q H
QH
Division of Neurology, Medical College of Ohio, Toledo 43614-0008, USA.
Futrell
N
N
Chen
F J
FJ
D000818:Animals; D001921:Brain / Q000276:immunology*; D002545:Brain Ischemia / Q000276:immunology*; D002536:Cerebral Arteries; D017931:DNA Primers; D007375:Interleukin-1 / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D017931:DNA Primers; D007375:Interleukin-1; D007376:Interleukin-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10