Cerebrospinal Fluid Cytokines and Chemokines Involved in Cytotoxic Cell Function and Risk of Acute 14-Day Mortality in Persons with Advanced HIV and Cryptococcal Meningitis

Abstract

Abstract Background The role of the immune response in acute mortality of cryptococcal meningitis remains unclear. Methods Cerebrospinal fluid (CSF) from 337 Ugandans with first-episode cryptococcal meningitis was collected. CSF cytokines and chemokines were quantified and compared by 14-day survival, stratification by quartiles, and logistical regression to determine association with acute mortality. Results Eighty-four (24.9%) participants died by day 14. Persons who survived to day 14 had higher levels of proinflammatory macrophage inflammatory protein (MIP)-3β and interferon (IFN)-β and cytotoxicity-associated granzyme B and inteferon gamma-induced protein (IP)-10 compared to those who died (P < .05 for each). Logistic regression analysis revealed that per 2-fold increase in proinflammatory interleukin (IL)-6, IL-1α, MIP-1β, MIP-3β, and IFN-β and cytotoxicity-associated IL-12, tumor necrosis factor–α, granzyme-B, and IP-10 CSF concentrations, the risk of acute 14-day mortality decreased. Similar biomarkers were implicated when stratified by quartiles and further identified that lower concentrations of anti-inflammatory IL-10 and IL-13 were associated with 14-day mortality (P < .05 for each). Conclusions Proinflammatory and cytotoxicity-associated cytokine and chemokine responses in the CSF decrease the risk of acute 14-day mortality. These data suggest that a cytotoxic immune environment in the CSF could potentially improve acute survival. Further research on cytotoxic cells is crucial to improve understanding of innate and adaptive immune responses in cryptococcal meningitis.