Castro J E Z, Vado-Solis I, Perez-Osorio C, Fredeking T M
Centro de Investigaciones Regionales Dr. Hideyo Noguchi, Universidad Autónoma de Yucatan, Mérida, YUC, Mexico.
Clin Dev Immunol. 2011;2011:370872. doi: 10.1155/2011/370872. Epub 2011 Mar 28.
Dengue virus infection can lead to dengue fever (DF) or dengue hemorrhagic fever (DHF). Disease severity has been linked to an increase in various cytokine levels. In this study, we evaluated the effectiveness of doxycycline and tetracycline to modulate serum levels of IL-6, IL-1B, and TNF and cytokine receptor/receptor antagonist TNF-R1 and IL-1RA in patients with DF or DHF. Hospitalized patients were randomized to receive standard supportive care or supportive care combined with doxycycline or tetracycline therapy. Serum cytokine and cytokine receptor/antagonist levels were determined at the onset of therapy and after 3 and 7 days. Cytokine and cytokine receptor/antagonist levels were substantially elevated at day 0. IL-6, IL-1β, and TNF remained at or above day 0 levels throughout the study period in untreated patients. Treatment with tetracycline or doxycycline resulted in a significant decline in cytokine levels. Similarly, IL-1RA and TNF-R1 serum concentrations were elevated at baseline and showed a moderate increase among untreated patients. Both drugs resulted in a significant rise in IL-1Ra levels by day 3 in patients. In contrast, treatment did not affect a similar result for TNF-R1. When compared to the control group, however, a significant rise post-treatment was seen upon intragroup analysis. Further analysis demonstrated that doxycycline was significantly more effective at modulating cytokine and cytokine receptor/antagonist levels than tetracycline.
登革病毒感染可导致登革热（DF）或登革出血热（DHF）。疾病严重程度与多种细胞因子水平升高有关。在本研究中，我们评估了强力霉素和四环素对调节DF或DHF患者血清中白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、肿瘤坏死因子（TNF）以及细胞因子受体/受体拮抗剂肿瘤坏死因子受体1（TNF-R1）和白细胞介素-1受体拮抗剂（IL-1RA）水平的有效性。住院患者被随机分为接受标准支持治疗或支持治疗联合强力霉素或四环素治疗。在治疗开始时以及治疗3天和7天后测定血清细胞因子和细胞因子受体/拮抗剂水平。在第0天，细胞因子和细胞因子受体/拮抗剂水平大幅升高。在整个研究期间，未治疗患者的IL-6、IL-1β和TNF水平维持在第0天水平或以上。四环素或强力霉素治疗导致细胞因子水平显著下降。同样，IL-1RA和TNF-R1血清浓度在基线时升高，在未治疗患者中呈适度上升。两种药物均使患者在第3天时IL-1Ra水平显著升高。相比之下，治疗对TNF-R1未产生类似效果。然而，与对照组相比，组内分析显示治疗后有显著升高。进一步分析表明，在调节细胞因子和细胞因子受体/拮抗剂水平方面，强力霉素比四环素显著更有效。
