Gene expression of IL-10 in relationship to TNF-α, IL-1β and IL-2 in the rat brain following middle cerebral artery occlusion

Abstract

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-α), interleukin-1 beta (IL-1β) 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-α and IL-1β mRNA increased at 2 h following MCAO and peaked at 6 h, with IL-10 mRNA detected only at 6 h. Contralaterally, both TNF-α and IL-1β 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-α, IL-1β gene expression is induced early following MCAO. The temporal profile of these cytokines is similar to that seen in sepsis, where TNF-α induces IL-10; subsequently IL-10 inhibits TNF-α 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-α production in ischemic brain tissue. The factors inducing contralateral expression of the inflammatory cytokines, TNF-α and IL-1β, along with the potential clinical significance of this remote cytokine gene expression, merit further study.