Serum cytokines associated with severity and complications of kala-azar
Serum cytokines associated with severity and complications of kala-azar
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DOI：
10.1179/2047773213y.0000000078
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发表时间：
2013-03-01
影响因子：
3.4
通讯作者：
Barral, Aldina P.
中科院分区：
文献类型：
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作者：
Costa, Dorcas L.;Rocha, Regina L.;Barral, Aldina P.
目的：最近的临床数据表明，严重的黑热病（或内脏利什曼病）是一种由炎性细胞因子介导的夸大的先天免疫反应，导致类似于疟疾，败血症和其他疾病中观察到的全身炎症综合征。我们测试了这一假设，通过测量血清细胞因子与黑热病individuals.Methods：我们比较了严重的黑热病患者（即出血表现，n=38）与患者没有出血的证据（n596）。我们进行了详细的临床和实验室评估，测量血清IL-1 β，IL-6，IL-8，IL-10，IL-12，干扰素-γ和TNF-α，和弥散性血管内凝血（DIC）的标志物。结果：婴儿有较高水平的炎症细胞因子，而HIV感染患者有较低浓度的IL-10和干扰素-γ。在死亡患者中发现了较高水平的IL-6、干扰素-γ和IL-8。IL-8和干扰素-γ与出血独立相关。几种细胞因子与严重临床和实验室表现的不同体征相关，包括DIC。IL-6与IL-1 β、IL-8、IL-10呈高度正相关，与TNF-α呈负相关。IL-1 β和TNF-α也高度独立相关的疾病severity.Conclusion：在其严重的形式，黑热病，一种被忽视的热带疾病，启动全身炎症反应，导致DIC和其他表现。儿童可能有更高的死亡风险，由于更强烈的细胞因子释放。这些数据支持IL-6是与致死性疾病相关的中心细胞因子的观点，但干扰素-γ、IL-1 β、IL-8和TNF-α也与疾病的严重程度有关。IL-6的抑制是这种疾病的严重或儿科形式的辅助治疗的潜在靶点。
Objectives: Recent clinical data suggest that severe kala-azar (or visceral leishmaniasis) is an exaggerated innate immune response mediated by inflammatory cytokines, leading to a systemic inflammatory syndrome similar to what is observed in malaria, sepsis and other diseases. We tested this hypothesis by measuring serum cytokines in individuals with kala-azar.Methods: We compared patients with severe kala-azar (i.e. hemorrhagic manifestations, n=38) with patients without evidence of hemorrhage (n596). We conducted a detailed clinical and laboratory evaluation, measuring serum IL-1beta, IL-6, IL-8, IL-10, IL-12, interferon-gamma, and TNF-alpha, and markers of disseminated intravascular coagulation (DIC).Results: Infants had higher levels of inflammatory cytokines, while HIV-infected patients had lower concentrations of IL-10 and interferon-gamma. Higher levels of IL-6, interferon-gamma, and IL-8 were found among deceased patients. IL-8 and interferon-gamma were independently associated with bleeding. Several cytokines were associated with different signs of severe clinical and laboratory manifestations, including DIC. IL-6 was highly positively and independently associated with IL-1beta, IL-8, IL-10, and negatively associated with TNF-alpha. IL-1beta and TNF-alpha were also highly independently associated with disease severity.Conclusion: In its severe form, kala-azar, a neglected tropical disease, initiates a systemic inflammatory response that leads to DIC and other manifestations. Children may have higher risk of death due to the more intense cytokine release. The data supports the notion that IL-6 is the central cytokine that is associated with lethal disease, but interferon-gamma, IL1beta, IL-8, and TNF-alpha are also involved with disease severity. Inhibition of IL-6 is a potential target of adjuvant therapy for severe or pediatric forms of this disease.