Japanese encephalitis virus up-regulates expression of macrophage migration inhibitory factor (MTF) mRNA in the mouse brain

Macrophage migration inhibitory factor (MIF) is known as a proinflammatory cytokine, glucocorticoid-induced immunomodulator, and pituitary hormone, an d contributes to broad-spectrum immune and inflammatory response. To invest igate the expression of MIF in the central nervous system in an event of vi ral infection, we evaluated MIF mRNA expression in the mouse brain infected with Japanese encephalitis virus (JEV). In situ hybridization revealed tha t MIF mRNA expression was significantly up-regulated in the whole brain by intracranial JEV inoculation at 2 days post-inoculation (d.p.i.). Neurons a s well as glial cells expressed MIF transcripts in which some of these cell s were co-labeled by double staining for JEV antigens and MIF mRNA. At 4 d. p.i., when typical symptoms of encephalitis were observed, JEV antigen-posi tive cells were much increased in parallel with enhanced MIF mRNA, consiste nt with the results of Northern blot analysis. Reverse transcription-polyme rase chain reaction showed that MIF mRNA was minimally changed at 1 d.p.i, in comparison with that at 0 d.p.i., but markedly up-regulated after 2 d.p. i. and sustained up to 4 d.p.i, On the other hand, a significant increase o f tumor necrosis factor (TNF)-alpha mRNA was observed after only 3 d.p.i. T hese data suggest the possibility that MIF is involved in virus-induced enc ephalitis with regard to not only immune responses in the early stage, but also the exacerbation of inflammation in concert with TNF-alpha in the late stages. This is the first evidence demonstrating that MIF is up-regulated in the case of virus-induced encephalitis, which should contribute to the f urther understanding of the pathological mechanism of JEV-induced encephali tis. (C) 2000 Elsevier Science B.V. All rights reserved.