Cerebrospinal Fluid Cytokine and Chemokine Patterns in Central Nervous System Infections, Hemorrhage and Neoplasms

Cytokines and chemokines are soluble proteins that act as regulators of cellular functions throughout the body. Cytokines and chemokines released in the setting of various CNS disorders appear in the CSF compartment where determination of their levels can provide insight into pathogenic processes such as neuroinflammation. We utilized the Millipore HCYTOMAG 60K assay/kit/system to perform multiplex profiling of 42 different cytokines/chemokines in the CSF of patients with a variety of distinct CNS disease processes, including infection, hemorrhage and neoplasia. CNS infections included viral (Chronic Parechovirus type 3 (HPeV3), Enterovirus (EV) 68, Adenovirus, JC virus, West Nile virus), bacterial (Mycobacterium tuberculosis, Borrelia burgdorferi, Propionibacterium acnes, Staphylococcus epidermidis, Streptococcus sp.), fungal (Cryptococcus neoformans) and single celled parasite (Toxoplasma gondii). CSF specimens negative for infectious organisms in noninflammatory conditions were selected as controls. Additional non-infectious samples tested were obtained from patients with subarachnoid hemorrhage (SAH) and following surgery for glioblastoma. The glioblastoma samples were noteworthy in having negligible elevations in the cytokines/chemokines tested. CSF from patients with SAH was elevated in only MCP-1/CCL2. Distinct patterns of cytokine/chemokine expression were detected for each infectious patient population. Picornavirus infections HPeV3 and EV68 were associated with increased levels of the monocyte chemoattractant protein MCP-1/CCL2 when compared to non-infectious, non-inflammatory samples. In contrast to chronic HPeV3 infection, EV68 encephalitis was associated with increased CSF levels of additional cytokines; CCLX1, IL-4 and IL-7. Adenovirus infection was associated with markedly higher levels of fractalkine in CSF when compared to any of the other non-inflammatory, infectious, hemorrhage or tumor cases. CSF from a Mycobacterium tuberculosis infection demonstrated increased levels of a greater variety of cytokines/chemokines than any of the other groups tested. Patterns of cytokine/chemokine expression in the CNS reveal characteristics of the host innate response that provide insight into the disease process and potential targets for therapeutic intervention