High numbers of perforin mRNA expressing CSF cells in multiple sclerosis patients with gadolinium-enhancing brain MRI lesions

Enhanced expression of pro- and anti-inflammatory cytokines is a common fin ding in MS, but attempts to correlate cytokine expression with disease acti vity have produced conflicting results. In this paper, gadolinium-(Gd-)enha ncing lesions on brain MRI were used as markers for active inflammation in patients with MS not treated with any immunomodulatory drugs. In parallel, in situ hybridization was used to detect blood and cerebrospinal fluid (CSF ) mononuclear cells (MNC) expressing cytokine mRNA. An association was obse rved between numbers of perforin mRNA expressing CSF MNC and numbers of Gd- enhancing brain MRT lesions. Perforin mRNA expressing CSF MNC were not dete cted in any of the patients lacking active lesions on brain MRI. The expres sion of tumor necrosis factor-alpha, interleukin-10 (IL-10) and IL-12 mRNA in CSF MNC did not differ between MS patients with and without active MRI l esions. Based on the present finding, a role for perforin in the disruption of the blood-brain barrier in MS can be hypothesized.