Magnetic resonance imaging reveals therapeutic effects of interferon-beta on cytokine-induced reactivation of rat model of multiple sclerosis

作者：Serres Sebastien; Bristow Claire; de Pablos Rocio M; Merkler Doron; Soto Manuel Sarmiento; Sibson Nicola R^*; Anthony Daniel C

来源：Journal of Cerebral Blood Flow and Metabolism, 2013, 33(5): 744-753.

DOI：10.1038/jcbfm.2013.12

• demyelination
• EAE
• inflammation
• IL-1 beta
• MRI
• multiple sclerosis
• rCBV

Interferon-beta (IFN-beta) drugs are considered to derive their beneficial effects on multiple sclerosis (MS) progression via their antiinflammatory properties, but the precise mechanism of action remains unclear. Here, we sought to discover how IFN-beta impacts on inflammation-associated aggravation of MS-like lesions in rat. Animals with dormant focal experimental allergic encephalomyelitis (EAE) lesions were challenged intravenously with a replication-deficient adenovirus vector carrying interleukin (IL)-1 beta cDNA (AdIL-1 beta). Aggravation of inflammation and demyelination within the focal EAE lesion was observed after AdIL-1 beta injection with associated changes in tissue structure detected by diffusion and magnetization transfer imaging. Postgadolinium-DTPA T-1-weighted images revealed contrast enhancement in the ipsilateral meninges, indicating breakdown of the blood-cerebrospinal fluid barrier, and increased left/right regional cerebral blood volume ratio was also observed after AdIL-1 beta injection. To determine the role of IFN-beta on reactivation of the EAE lesion, rats were treated with therapeutic doses of IFN-beta and focal EAE lesions showed significantly reduced reactivation in response to systemic AdIL-1 beta injection. In conclusion, these findings indicate a central role for peripheral IL-1 beta expression in the mechanism of MS lesion reactivation and that the therapeutic effects of IFN-beta may, at least in part, reflect suppression of the effects of peripheral inflammation on MS lesion pathogenesis.

• 出版日期2013-5