Current laboratory testing of cerebrospinal fluid (CSF) does not consistently discriminate between different central nervous system (
CNS) disease states. Rapidly distinguishing
CNS infections from other brain and
spinal cord disorders that share a similar clinical presentation is critical. New approaches focusing on aspects of disease biology, such as immune response profiles that can have stimulus-specific attributes, may be helpful. We undertook this preliminary proof-of-concept study using multiplex ELISA to measure CSF
cytokine levels in various CNS disorders (
infections, autoimmune/
demyelinating diseases,
lymphomas, and
gliomas) to determine the potential utility of
cytokine patterns in differentiating
CNS infections from other
CNS diseases. Both agglomerative hierarchical clustering and mixture discriminant analyses revealed grouping of
CNS disease types based on
cytokine expression. To further investigate the ability of CSF
cytokine levels to distinguish various
CNS disease states, non-parametric statistical analysis was performed. Mann-Whitney test analysis demonstrated that
CNS infections are characterized by significantly higher CSF lP-10/CXCL10 levels than the pooled non-infectious CNS disorders (p = 0.0001). Within the
infection group, elevated levels of MDC/CCL22 distinguished non-viral from
viral infections (p = 0.0048). Each disease group of the non-infectious CNS disorders independently showed IP-10/CXCL10 levels that are significantly lower than the
infection group [(autoimmune /
demyelinating disorders (p = 0.0005),
lymphomas (p = 0.0487),
gliomas (p = 0.0294), and controls (p = 0.0001)]. Additionally, of the
non-infectious diseases,
gliomas can be distinguished from
lymphomas by higher levels of GRO/CXCL1 (p = 0.0476), IL-7 (p = 0.0119), and IL-8 (p = 0.0460).
Gliomas can also be distinguished from autoimmune/
demyelinating disorders by higher levels of GRO/CXCL1 (p = 0.0044), IL-7 (p = 0.0035) and IL-8 (p = 0.0176). Elevated CSF levels of
PDGF-AA distinguish
lymphomas from autoimmune/demyelinating cases (p = 0.0130). Interrogation of the above comparisons using receiver operator characteristic analysis demonstrated area under the curve (AUC) values (ranging from 0.8636-1.0) that signify good to excellent utility as potential diagnostic discriminators. In conclusion, our work indicates that upon formal validation, measurement of CSF
cytokine levels may have clinical utility in both identifying a CNS disorder as infectious in etiology and, furthermore, in distinguishing viral from non-
viral CNS infections.