Severe visceral leishmaniasis in children: the relationship between cytokine patterns and clinical features

Introduction The relationship between severe clinical manifestations of visceral leishmaniasis (VL) and immune response profiles has not yet been clarified, despite numerous studies on the subject. This study aimed to investigate the relationship between cytokine profiles and the presence of immunological markers associated with clinical manifestations and, particularly, signs of severity, as defined in a protocol drafted by the Ministry of Health (Brazil). Methods We conducted a prospective, descriptive study between May 2008 and December 2009. This study was based on an assessment of all pediatric patients with VL who were observed in a reference hospital in Maranhão. Results Among 27 children, 55.5% presented with more than one sign of severity or warning sign. Patients without signs of severity or warning signs and patients with only one warning sign had the highest interferon-gamma (IFN-γ) levels, although their interleukin 10 (IL-10) levels were also elevated. In contrast, patients with the features of severe disease had the lowest IFN-γ levels. Three patients who presented with more than two signs of severe disease died; these patients had undetectable interleukin 2 (IL-2) and IFN-γ levels and low IL-10 levels, which varied between 0 and 36.8pg/mL. Conclusions Our results showed that disease severity was associated with low IFN-γ levels and elevated IL-10 levels. However, further studies with larger samples are needed to better characterize the relationship between disease severity and cytokine levels, with the aim of identifying immunological markers of active-disease severity.

引言 尽管已有诸多相关研究，但内脏利什曼病（visceral leishmaniasis, VL）重症临床表现与免疫应答特征之间的关联仍未阐明。本研究旨在探究细胞因子特征与临床表征相关免疫标志物的关联，尤其是参照巴西卫生部起草的指南所定义的重症体征间的关联。方法 本研究为前瞻性描述性研究，实施时间为2008年5月至2009年12月，研究对象为马拉尼昂州某参考医院收治的全部儿童内脏利什曼病患者。结果 27名患儿中，55.5%出现至少1项重症体征或预警征象。无重症体征或预警征象、仅出现1项预警征象的患儿，其干扰素-γ（interferon-gamma, IFN-γ）水平最高，同时白细胞介素10（interleukin 10, IL-10）水平亦有所升高。与之相反，具备重症疾病特征的患儿，其干扰素-γ水平最低。3名出现2项以上重症体征的患儿死亡，此类患者的白细胞介素2（interleukin 2, IL-2）与干扰素-γ水平无法检出，白细胞介素10水平较低，介于0至36.8pg/mL之间。结论 本研究结果显示，疾病严重程度与低干扰素-γ水平及升高的白细胞介素10水平相关。不过，仍需开展更大样本量的后续研究，以进一步明确疾病严重程度与细胞因子水平之间的关联，旨在识别活动性疾病重症的免疫标志物。