PDF(Pubmed)
Abstract：
Severe Legionnaires\' disease (LD) can lead to multi-organ failure or death in 10%-30% of patients. Although hyper-inflammation and immunoparalysis are well described in sepsis and are associated with high disease severity, little is known about the immune response in LD. This study aimed to evaluate the immune status of patients with LD and its association with disease severity.
A total of 92 hospitalized LD patients were included; 19 plasmatic cytokines and pulmonary Legionella DNA load were measured in 84 patients on the day of inclusion (day 0, D0). Immune functional assays (IFAs) were performed from whole blood samples collected at D2 and stimulated with concanavalin A [conA, n = 19 patients and n = 21 healthy volunteers (HV)] or lipopolysaccharide (LPS, n = 14 patients and n = 9 HV). A total of 19 cytokines (conA stimulation) and TNF-α (LPS stimulation) were quantified from the supernatants. The Sequential Organ Failure Assessment (SOFA) severity score was recorded at D0 and the mechanical ventilation (MV) status was recorded at D0 and D8.
Among the 84 patients, a higher secretion of plasmatic MCP-1, MIP1-β, IL-6, IL-8, IFN-γ, TNF-α, and IL-17 was observed in the patients with D0 and D8 MV. Multiparametric analysis showed that these seven cytokines were positively associated with the SOFA score. Upon conA stimulation, LD patients had a lower secretion capacity for 16 of the 19 quantified cytokines and a higher release of IL-18 and MCP-1 compared to HV. IL-18 secretion was higher in D0 and D8 MV patients. TNF-α secretion, measured after ex vivo LPS stimulation, was significantly reduced in LD patients and was associated with D8 MV status.
The present findings describe a hyper-inflammatory phase at the initial phase of Legionella pneumonia that is more pronounced in patients with severe LD. These patients also present an immunoparalysis for a large number of cytokines, except IL-18 whose secretion is increased. An assessment of the immune response may be relevant to identify patients eligible for future innovative host-directed therapies.
A total of 92 hospitalized LD patients were included; 19 plasmatic cytokines and pulmonary Legionella DNA load were measured in 84 patients on the day of inclusion (day 0, D0). Immune functional assays (IFAs) were performed from whole blood samples collected at D2 and stimulated with concanavalin A [conA, n = 19 patients and n = 21 healthy volunteers (HV)] or lipopolysaccharide (LPS, n = 14 patients and n = 9 HV). A total of 19 cytokines (conA stimulation) and TNF-α (LPS stimulation) were quantified from the supernatants. The Sequential Organ Failure Assessment (SOFA) severity score was recorded at D0 and the mechanical ventilation (MV) status was recorded at D0 and D8.
Among the 84 patients, a higher secretion of plasmatic MCP-1, MIP1-β, IL-6, IL-8, IFN-γ, TNF-α, and IL-17 was observed in the patients with D0 and D8 MV. Multiparametric analysis showed that these seven cytokines were positively associated with the SOFA score. Upon conA stimulation, LD patients had a lower secretion capacity for 16 of the 19 quantified cytokines and a higher release of IL-18 and MCP-1 compared to HV. IL-18 secretion was higher in D0 and D8 MV patients. TNF-α secretion, measured after ex vivo LPS stimulation, was significantly reduced in LD patients and was associated with D8 MV status.
The present findings describe a hyper-inflammatory phase at the initial phase of Legionella pneumonia that is more pronounced in patients with severe LD. These patients also present an immunoparalysis for a large number of cytokines, except IL-18 whose secretion is increased. An assessment of the immune response may be relevant to identify patients eligible for future innovative host-directed therapies.
摘要：
■严重军团病（LD）可导致10％-30％的患者多器官衰竭或死亡。尽管高炎症和免疫麻痹在脓毒症中有很好的描述，并且与高疾病严重程度相关。对LD的免疫反应知之甚少。本研究旨在评估LD患者的免疫状态及其与疾病严重程度的关系。
■共纳入92例住院LD患者；在纳入当天（第0天，第0天），在84例患者中测量了19种血浆细胞因子和肺军团菌DNA负荷。从D2收集的全血样品中进行免疫功能测定（IFAs），并用伴刀豆球蛋白A[conA，n=19名患者和n=21名健康志愿者（HV）]或脂多糖（LPS，n=14例，n=9HV）。从上清液中定量总共19种细胞因子(conA刺激)和TNF-α(LPS刺激)。在D0记录序贯器官衰竭评估(SOFA)严重程度评分,并且在D0和D8记录机械通气(MV)状态。
■在84名患者中，血浆MCP-1，MIP1-β的较高分泌，IL-6，IL-8，IFN-γ，TNF-α,在D0和D8MV患者中观察到IL-17。多参数分析表明，这7种细胞因子与SOFA评分呈正相关。在ConA刺激下，与HV相比，LD患者对19种定量细胞因子中的16种具有较低的分泌能力，而IL-18和MCP-1的释放更高。D0和D8MV患者IL-18分泌较高。TNF-α分泌，离体LPS刺激后测量，在LD患者中显著降低，并与D8MV状态相关。
■本研究结果描述了军团菌肺炎初始阶段的过度炎症阶段，这在患有严重LD的患者中更为明显。这些患者还表现出大量细胞因子的免疫麻痹，除了分泌增加的IL-18。对免疫反应的评估可能与确定有资格接受未来创新的宿主导向疗法的患者有关。
■共纳入92例住院LD患者；在纳入当天（第0天，第0天），在84例患者中测量了19种血浆细胞因子和肺军团菌DNA负荷。从D2收集的全血样品中进行免疫功能测定（IFAs），并用伴刀豆球蛋白A[conA，n=19名患者和n=21名健康志愿者（HV）]或脂多糖（LPS，n=14例，n=9HV）。从上清液中定量总共19种细胞因子(conA刺激)和TNF-α(LPS刺激)。在D0记录序贯器官衰竭评估(SOFA)严重程度评分,并且在D0和D8记录机械通气(MV)状态。
■在84名患者中，血浆MCP-1，MIP1-β的较高分泌，IL-6，IL-8，IFN-γ，TNF-α,在D0和D8MV患者中观察到IL-17。多参数分析表明，这7种细胞因子与SOFA评分呈正相关。在ConA刺激下，与HV相比，LD患者对19种定量细胞因子中的16种具有较低的分泌能力，而IL-18和MCP-1的释放更高。D0和D8MV患者IL-18分泌较高。TNF-α分泌，离体LPS刺激后测量，在LD患者中显著降低，并与D8MV状态相关。
■本研究结果描述了军团菌肺炎初始阶段的过度炎症阶段，这在患有严重LD的患者中更为明显。这些患者还表现出大量细胞因子的免疫麻痹，除了分泌增加的IL-18。对免疫反应的评估可能与确定有资格接受未来创新的宿主导向疗法的患者有关。
