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Cytokine patterns in a prospective cohort of HIV-infected patients with cryptococcal meningitis following initiation of antifungal and antiretroviral therapy

机译：在开始抗真菌和抗逆转录病毒治疗后HIV感染隐球菌脑膜炎患者的预期队列中的细胞因子模式

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Cryptococcal meningitis (CM) is a life-threatening infection in HIV-infected patients, especially in resource-limited settings. Cytokine patterns in the cerebrospinal fluid (CSF) and sera may be related to clinical outcomes. This study aimed to evaluate cytokine patterns in the CSF and sera of HIV-infected patients with CM as well as the cytokines produced by peripheral blood mononuclear cells (PBMCs) when stimulated with LPS and cryptococcal GXM. CSF and serum levels of IL-2, IL-4, IL-8, IL-10, IL-12p40, IL-17A, INF-γ, TNF-α and CXCL-10 were measured in HIV-infected patients with CM (CM+ HIV+) at various time points. Cytokine levels were evaluated in the PBMC culture supernatants and the baseline values were compared to those of HIV-infected patients without CM (CM- HIV+) and healthy controls (CM- HIV-). CSF cytokine levels at admission (n = 33) were higher than levels among the 23 survivors at week 2, but statistically significant differences were observed for IL-8 and IFN-γ (p<0.05). CSF and serum levels of IL-4 and IL-17A at week 10 (n = 16) were lower than the baseline values, whereas IL-2 levels increased compared to week 2 (p<0.05). At week 16 (n = 15), CSF and serum levels of IL-4, IL-10 and CXCL-10 were decreased compared to the baseline values (p<0.05). PBMCs from CM- HIV- individuals produced significantly higher levels of proinflammatory cytokines in response to LPS, with the exception of TNF-α, which showed higher levels among CM+ HIV+ patients. The PBMCs of CM patients produced higher levels of IL-4 than those of CM- HIV- patients in response to GXM stimulation, and levels progressively decreased during treatment (p<0.05). Then, a progressive shift in cytokine expression favoring a Th1 pattern was observed, which is crucial in controlling cryptococcal infection. A better understanding of the protective immune response against Cryptococcus neoformans will help to develop novel strategies to improve the outcomes of patients with cryptococcosis.
机译：隐球菌性脑膜炎（CM）在HIV感染的患者中是威胁生命的感染，尤其是在资源有限的环境中。脑脊液（CSF）和血清中的细胞因子类型可能与临床结局有关。这项研究旨在评估受LPS和隐球菌GXM刺激的HIV感染的CM患者的CSF和血清中的细胞因子模式，以及外周血单核细胞（PBMC）产生的细胞因子。在感染HIV的CM患者中测量CSF和血清IL-2，IL-4，IL-8，IL-10，IL-12p40，IL-17A，INF-γ，TNF-α和CXCL-10的水平（ CM + HIV + ）。在PBMC培养上清液中评估细胞因子水平，并将基线值与未感染CM（CM - HIV + ）和健康对照组（CM < sup>- HIV -）。入院时的脑脊液细胞因子水平（n = 33）高于第2周的23名幸存者中的水平，但在IL-8和IFN-γ上观察到统计学显着差异（p <0.05）。第10周（n = 16）的CSF和血清IL-4和IL-17A水平低于基线值，而IL-2水平则比第2周增加（p <0.05）。与基线值相比，第16周（n = 15）时，CSF和IL-4，IL-10和CXCL-10的血清水平降低（p <0.05）。来自CM - HIV -个体的PBMC响应LPS产生的促炎细胞因子水平明显升高，但TNF-α除外，后者在CM + HIV + 患者。响应GXM刺激，CM患者的PBMC产生的IL-4水平高于CM - HIV -患者，并且在治疗期间该水平逐渐降低（p <0.05 ）。然后，观察到细胞因子表达的逐步变化有利于Th1型，这在控制隐球菌感染中至关重要。更好地理解针对新型隐球菌的保护性免疫应答将有助于开发新的策略，以改善隐球菌病患者的预后。

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