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. 2016 Jun 13;3(4):e246.
doi: 10.1212/NXI.0000000000000246. eCollection 2016 Aug.

Proinflammatory cytokines and matrix metalloproteinases in CSF of patients with VZV vasculopathy

Dallas Jones  1 , Enrique Alvarez  1 , Sean Selva  1 , Don Gilden  1 , Maria A Nagel  1
Affiliations

Proinflammatory cytokines and matrix metalloproteinases in CSF of patients with VZV vasculopathy

Dallas Jones et al. Neurol Neuroimmunol Neuroinflamm. .

Abstract

Objective: To determine the levels of proinflammatory cytokines and matrix metalloproteinases (MMPs) in the CSF of patients with virologically verified varicella zoster virus (VZV) vasculopathy.

Methods: CSF from 30 patients with virologically verified VZV vasculopathy was analyzed for levels of proinflammatory cytokines and MMPs using the Meso Scale Discovery multiplex ELISA platform. Positive CNS inflammatory disease controls were provided by CSF from 30 patients with multiple sclerosis. Negative controls were provided by CSF from 20 healthy controls.

Results: Compared to multiple sclerosis CSF and CSF from healthy controls, levels of interleukin (IL)-8, IL-6, and MMP-2 were significantly elevated in VZV vasculopathy CSF.

Conclusions: CSF of patients with VZV vasculopathy revealed a unique profile of elevated proinflammatory cytokines, IL-8 and IL-6, along with elevated MMP-2. The relevance of these cytokines to the pathogenesis of VZV vasculopathy requires further study.

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Figures

Figure 1.
Figure 1.. Cytokine levels in CSF from patients with VZV vasculopathy, patients with MS, and from healthy controls
Levels of IL-8 (p < 0.0001), IL-6 (p = 0.007) and (H) IL-12p70 (p = 0.011) were significantly higher in VZV vasculopathy CSF than those in MS CSF. Compared to CSF from healthy controls, (A) IL-8 (p < 0.0001), (B) IL-6 (p = 0.0001), (C) IFNγ (p = 0.0004), (D) TNF-α (p = 0.0012), (E) IL-1β (p = 0.006), and (F) IL-2 (p = 0.01) levels were significantly higher in VZV vasculopathy CSF, and levels of IL-8 (p < 0.004), IL-6 (p = 0.002), IFNγ (p < 0.0001), TNF-α (p < 0.0001), IL-1β (p < 0.0001), IL-2 (p < 0.0001), and (G) IL-10 (p < 0.0001) were significantly higher in MS CSF. (I) IL-4 and (J) IL-13 levels did not differ significantly among the 3 groups. Each dot represents cytokine values for individual patients; solid bars represent median CSF cytokine levels for each group. Dotted lines represent lower limits of detection for each cytokine. The asterisk represents statistically significant differences in median cytokine levels among the 3 groups. IFNγ = interferon gamma; IL = interleukin; MS = multiple sclerosis; TNF-α = tumor necrosis factor α; VZV = varicella zoster virus.
Figure 2.
Figure 2.. MMP levels in CSF from patients with VZV vasculopathy, patients with MS, and from healthy controls
MMP-2 levels were significantly higher in VZV vasculopathy CSF than those in MS CSF (p = 0.0001). Compared to CSF from healthy controls, levels of (A) MMP-1 (p = 0.0002), (B) MMP-2 (p = 0.0001), (C) MMP-3 (p = 0.0002), (D) MMP-9 (p < 0.0001), and (E) MMP-10 (p < 0.0001) were significantly higher in VZV vasculopathy, and levels of MMP-1 (p = 0.0009), MMP-2 (p = 0.0001), MMP-3 (p < 0.0001), MMP-9 (p < 0.0001), and MMP-10 (p < 0.0001) were significantly increased in CSF from patients with MS. Each dot represents MMP values from an individual patient, and solid bars represent median CSF MMP levels for each group. Dotted lines represent lower limits of detection for each MMP. The asterisk represents statistically significant differences in median MMP levels among the 3 groups. MMP = matrix metalloproteinase; MS = multiple sclerosis; VZV = varicella zoster virus.
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References

    1. Nagel MA, Traktinskiy I, Azarkh Y, et al. . Varicella zoster virus vasculopathy: analysis of virus-infected arteries. Neurology 2011;77:364–370. - PMC - PubMed
    1. Nagel MA, Traktinskiy I, Stenmark KR, Frid MG, Choe A, Gilden D. Varicella-zoster virus vasculopathy: immune characteristics of virus-infected arteries. Neurology 2013;80:62–68. - PMC - PubMed
    1. Nagel MA, Forghani B, Mahalingam R, et al. . The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy. Neurology 2007;68:1069–1073. - PubMed
    1. Stevens DA, Ferrington RA, Jordan GW, Merigan TC. Cellular events in zoster vesicles: relation to clinical course and immune parameters. J Infect Dis 1975;131:509–515. - PubMed
    1. Haug A, Mahalingam R, Cohrs RJ, Schmid DS, Corboy JR, Gilden D. Recurrent polymorphonuclear pleocytosis with increased red blood cells caused by varicella zoster virus infection of the central nervous system: case report and review of the literature. J Neurol Sci 2010;292:85–88. - PMC - PubMed