Correlation between blood and CSF compartment cytokines and chemokines in subjects with cryptococcal meningitis.

Background: Though peripheral blood is a crucial sample to study immunology, it is unclear whether the immune environment in the peripheral vasculature correlates with that at the end-organ site of infection. Utilizing cryptococcal meningitis as a model, we investigated the correlation between serum and cerebrospinal fluid biomarkers over time. Methodology and Principal Findings: We analyzed the cerebrospinal fluid and serum of 160 subjects presenting with first episode cryptococcal meningitis for soluble cytokines and chemokines measured by Luminex assay. Specimens were collected at meningitis diagnosis, 1-week, and 2-weeks post cryptococcal diagnosis. We compared paired samples by Spearman correlation and the p-value was set at <0.01. Of the 21 analytes tested at baseline, there was no correlation detected between nearly all analytes. A weak negative correlation was found between serum and cerebrospinal fluid levels of interferon-gamma (Rho= −0.214, p= .007) and interleukin- 4 (Rho= −0.232, p= .003). There was no correlation at 1-week post cryptococcal diagnosis. However, at 2-weeks post diagnosis, there was a weak positive correlation between levels of granulocyte-macrophage colony-stimulating factor (Rho= 0.25, p= .007) between serum and cerebrospinal fluid. No cytokine or chemokine showed consistent correlation overtime. Conclusion and Significance: Based on our analysis of 21 biomarkers, serum and cerebrospinal fluid immune responses do not correlate. There appears to be a distinct immune environment in terms of soluble biomarkers in the vasculature versus end-organ site of infection. While this is a model of HIV-related cryptococcal meningitis, we postulate that assuming the blood compartment is representative of the immune function at the end-organ site of infection may not be appropriate.