Kuruppu Heshan, Wickramanayake W P Rivindu H, Jeewandara Chandima, Peranantharajah Deneshan, Colambage Hashini S, Perera Lahiru, Gomes Laksiri, Wijewickrama Ananda, Ogg Graham S, Malavige Gathsaurie Neelika
AICBU, Department of Immunology and Molecular Medicine, University of Sri Jayewardenepura, Nugegoda, Sri Lanka.
National Institute of Infectious Diseases, Angoda, Sri Lanka.
medRxiv. 2023 Jan 9:2023.01.06.23284269. doi: 10.1101/2023.01.06.23284269.
Adipokines have not been studied in acute dengue, despite their emerging role in inducing and regulating inflammation. Therefore, we sought to identify adipokine levels in patients with varying severities of acute dengue to understand their role in disease pathogenesis. We determined the levels of leptin, resistin, omentin, adiponectin, as well as IFNβ, and NS1 using quantitative ELISA in patients with dengue fever (DF=49) and dengue haemorrhagic fever (DHF=22) at admission (febrile phase) and at the time of discharge (recovery phase). The viral loads and serotypes of all samples were quantified using quantitative real-time RT-PCR. Resistin levels (p =0.04) and omentin (p=0.006) levels were significantly higher in patients who developed DHF. Omentin levels in the febrile phase also correlated with the AST (Spearman's r=0.38, p=0.001) and ALT levels (Spearman's r=0.24, p=0.04); as well as serum leptin levels with both AST (Spearman's r=0.27, p=0.02) and ALT (Spearman's r=0.28, p=0.02). Serum adiponectin levels in the febrile phase did not correlate with any of the other adipokines or with liver enzymes, but inversely correlated with CRP levels (Spearman's r=-0.31, p=0.008). Although not significant (p=0.14) serum IFNβ levels were lower in the febrile phase in those who progressed to develop DHF (median 0, IQR 0 to 39.4 pg/ml), compared to those who had DF (median 37.1, IQR 0 to 65.6 pg.ml). The data suggest that adipokines are likely to play a role in the pathogenesis of dengue, which should be further explored for the potential to be used as prognostic markers and as therapeutic targets.
尽管脂肪因子在诱导和调节炎症方面的作用日益凸显,但尚未在急性登革热中进行研究。因此,我们试图确定不同严重程度的急性登革热患者体内的脂肪因子水平,以了解它们在疾病发病机制中的作用。我们使用定量酶联免疫吸附测定法(ELISA),测定了登革热患者(登革热发热[DF]=49例)和登革出血热患者(DHF=22例)在入院时(发热期)和出院时(恢复期)的瘦素、抵抗素、网膜素、脂联素以及IFNβ和NS1的水平。使用定量实时逆转录聚合酶链反应(RT-PCR)对所有样本的病毒载量和血清型进行了定量分析。发生登革出血热的患者体内抵抗素水平(p =0.04)和网膜素水平(p=0.006)显著更高。发热期的网膜素水平也与谷草转氨酶(Spearman相关系数r=0.38,p=0.001)和谷丙转氨酶水平(Spearman相关系数r=0.24,p=0.04)相关;血清瘦素水平与谷草转氨酶(Spearman相关系数r=0.27,p=0.02)和谷丙转氨酶(Spearman相关系数r=0.28,p=0.02)均相关。发热期的血清脂联素水平与其他任何脂肪因子或肝酶均无相关性,但与CRP水平呈负相关(Spearman相关系数r=-0.31,p=0.008)。尽管差异不显著(p=0.14),但进展为登革出血热的患者在发热期的血清IFNβ水平(中位数为0,四分位距为0至39.4 pg/ml)低于患登革热发热的患者(中位数为37.1,四分位距为0至65.6 pg/ml)。数据表明,脂肪因子可能在登革热发病机制中发挥作用,应进一步探索其作为预后标志物和治疗靶点的潜力。