Ferreira Ralph Antonio Xavier, de Oliveira Solange Artimos, Gandini Mariana, Ferreira Laura da Cunha, Correa Gladys, Abiraude Fernanda Mattos, Reid Mariana Mancebo, Cruz Oswaldo Gonçalves, Kubelka Claire Fernandes
Disciplina de Doenças Infecciosas e Parasitárias, Hospital Universitário Antônio Pedro, Universidade, Federal Fluminense, Niterói, RJ, Brazil.
Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
Acta Trop. 2015 Sep;149:138-47. doi: 10.1016/j.actatropica.2015.04.023. Epub 2015 May 2.
Dengue fever is usually a benign acute viral infection transmitted by arthropods but may evolve to severe clinical manifestations such as coagulation and/or hemodynamic disorders, caused mainly by an increase of vascular permeability. Deregulated circulating immunological factors have been associated with severity. In Brazil severe cases appeared in children only recently and we evaluated the profile of cytokine/chemokine kinetics in 134 hospitalized young patients during the epidemic in Rio de Janeiro in 2008. Inflammatory cytokines TNF and IFNγ were found elevated during the acute phase in children as well as the anti-inflammatory IL10 and chemokines MIF and CXCL10/IP10, all last three persisting longer during the recovery phase. Severe disease fitting the dengue hemorrhagic fever pattern (WHO, 1997) was associated with higher IL10 and CXCL10/IP10 circulating levels (peak levels at seven days with P<0.01 and P<0.001 respectively as compared to DF). These factors were higher in patients pulmonary effusion or ascites (P<0.05 for IL10 and P<0.01 for CXCL10/IP10). Both factors were also associated with liver changes such as AST increase correlated with CXCL10/IP10 (r=0.4300 with P<0.0001) and patients presenting painful hepatomegaly showed higher circulating levels of IL10 (P<0.01, at 7-9 days) and of CXCL10/IP10 (P<0.05, 4-6 days and P<0.001, 7-9 days) when compared to patients without apparent liver alterations. Most cases presented a history of prior infection (93%). This is the first study demonstrating cytokine and chemokine association with severity during dengue fever in Brazilian children. IL10 and CXCL10/IP10 play a role in the disease severity associated with induction of vascular leakage and a novel association with changes in liver dysfunction.
登革热通常是一种由节肢动物传播的良性急性病毒感染，但可能会发展为严重的临床表现，如凝血和/或血液动力学紊乱，主要是由血管通透性增加引起的。失调的循环免疫因子与疾病严重程度有关。在巴西，严重病例直到最近才出现在儿童中，我们评估了2008年里约热内卢疫情期间134名住院年轻患者的细胞因子/趋化因子动力学特征。发现炎症细胞因子TNF和IFNγ在急性期儿童中升高，抗炎性细胞因子IL10以及趋化因子MIF和CXCL10/IP10也是如此，后三者在恢复期持续时间更长。符合登革出血热模式（世界卫生组织，1997年）的严重疾病与更高的IL10和CXCL10/IP10循环水平相关（与登革热相比，第7天的峰值水平分别为P<0.01和P<0.001）。这些因子在有胸腔积液或腹水的患者中更高（IL10为P<0.05，CXCL10/IP10为P<0.01）。这两个因子也与肝脏变化有关，如AST升高与CXCL10/IP10相关（r=0.4300，P<0.0001），与无明显肝脏改变的患者相比，出现肝肿大疼痛的患者IL10循环水平更高（第7 - 9天为P<0.01），CXCL10/IP10循环水平更高（第4 - 6天为P<0.05，第7 - 9天为P<0.001）。大多数病例有既往感染史（93%）。这是第一项证明巴西儿童登革热期间细胞因子和趋化因子与疾病严重程度相关的研究。IL10和CXCL10/IP10在与血管渗漏诱导相关的疾病严重程度中起作用，并与肝功能障碍变化存在新的关联。
