Chemokines and matrix metalloproteinases in cerebrospinal fluid of patients with central nervous system complications caused by varicella-zoster virus

Background: Varicella-zoster virus (VZV) is a common viral agent causing central nervous system (CNS) infections including encephalitis, meningitis, and Ramsay Hunt syndrome. Neurological complications occur frequently despite antiviral treatment. Matrix metalloproteinases (MMPs) and cytokines are involved in the neuroinflammatory response during CNS infection. Their role in VZV CNS infections and how they differ between different CNS entities caused by VZV are poorly investigated.

Methods: We analyzed the levels of 30 chemokines and 9 MMPs in cerebrospinal fluid (CSF) and serum from 66 patients with VZV CNS infections diagnosed by detection of VZV DNA in CSF and concomitant neurological symptoms and compared with a control group (n = 24).

Results: Levels of CCL19, CXCL8, CXCL9, and CXCL10 were significantly increased and surpassing the levels in serum when analyzing all patients with VZV CNS infections whereas CXCL11 was only increased in CSF of patients with VZV meningitis. MMP-2-levels were highly elevated in CSF of all 66 VZV patients. The patients with encephalitis had the most significantly increased levels of MMPs in CSF, and MMP-3, MMP-8, and MMP-12 were exclusively increased in this group, whereas MMP-9 in CSF was increased in the patients with VZV meningitis.

Conclusions: We show that both chemokines and MMPs are elevated in the CSF of patients with VZV CNS infections. Encephalitis and meningitis patients differed with respect to other chemokines (CXCL11) and MMPs (MMP-3, MMP-8, MMP-9, and MMP-12), indicating that different location of the virus gives rise to qualitative differences in the ensuing inflammatory response. In addition, the pronounced increase of MMPs in CSF of the patients with encephalitis suggests an association to the severity of this manifestation, compared to VZV meningitis and Ramsay Hunt syndrome. The role of MMPs in association to chemokines should be further investigated to evaluate their significance in the neuropathogenesis of VZV CNS infections and as a potential target for new treatment alternatives.