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.

中文翻译：

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脑脊液细胞因子和趋化因子参与晚期 HIV 和隐球菌性脑膜炎患者的细胞毒性细胞功能和急性 14 天死亡风险


背景 免疫反应在隐球菌性脑膜炎急性死亡率中的作用仍不清楚。方法 收集 337 例首发隐球菌性脑膜炎乌干达人的脑脊液 （CSF）。对 CSF 细胞因子和趋化因子进行量化，并通过 14 天生存率、四分位数分层和 logistical 回归进行比较，以确定与急性死亡率的相关性。结果 84 名 （24.9%） 参与者在第 14 天死亡。存活到第 14 天的人与死亡者相比，促炎巨噬细胞炎症蛋白 （MIP）-3β 和干扰素 （IFN）-β 以及细胞毒性相关的颗粒酶 B 和依特费隆 γ 诱导蛋白 （IP）-10 水平更高（P < .05）。Logistic 回归分析显示，促炎性白细胞介素 （IL）-6 、 IL-1α 、 MIP-1β 、 MIP-3β 和 IFN-β 和细胞毒性相关 IL-12 、肿瘤坏死因子-α、颗粒酶-B 和 IP-10 CSF 浓度每增加 2 倍，急性 14 d 死亡风险降低。当按四分位数分层时，类似的生物标志物涉及，并进一步确定较低浓度的抗炎 IL-10 和 IL-13 与 14 天死亡率相关 （P < .05）。结论 CSF 中的促炎和细胞毒性相关细胞因子和趋化因子反应可降低 14 天急性死亡的风险。这些数据表明，CSF 中的细胞毒性免疫环境可能会提高急性生存率。对细胞毒性细胞的进一步研究对于提高对隐球菌性脑膜炎先天性和适应性免疫反应的理解至关重要。