https://orcid.org/0000-0003-1495-4596
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Elizabeth C Okafor, Liliane Mukaremera, Kathy H Hullsiek, Nicole Engen, Lillian Tugume, Kenneth Ssebambulidde, Abdu K Musubire, Edwin Nuwagira, Edward Mpoza, Darlisha A Williams, Conrad Muzoora, Joshua Rhein, David B Meya, Kirsten Nielsen, David R Boulware, for the Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis (ASTRO-CM) Team, 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, The Journal of Infectious Diseases, Volume 231, Issue 2, 15 February 2025, Pages 521–531, https://doi.org/10.1093/infdis/jiae421
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Abstract
The role of the immune response in acute mortality of cryptococcal meningitis remains unclear.
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.
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).
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.
