Dengue Patients Treated with Doxycycline Showed Lower Mortality Associated to a Reduction in IL-6 and TNF Levels

OBJECTIVE: To determine the effect of doxycycline treatment on cytokine levels, including tumor necrosis factor (TNF) and interleukin 6 (IL-6), and mortality in dengue patients at high risk of complication. METHODS: A group of dengue hemorrhagic fever patients (n=231) were randomized to receive either standard supportive care or supportive care in addition to oral doxycycline twice daily for 7 days. Dengue virus infection was confirmed by PCR using multiple primers. Serum samples were obtained at days 0, 3, 5 and 7 and tested for levels of TNF and IL-6. RESULTS: Doxycycline-treated group presented a 46% lower mortality than that observed in the untreated group (11.2% 13/116 vs 20.9% 24/115, respectively, p=0.05). Moreover, administration of doxycycline resulted in a significant (p<0.01) decrease in levels of TNF and IL-6 versus controls in the tests performed during follow-up (day 3, 5 and 7). Patients who died in both groups possessed significantly (p<0.01) higher levels of TNF and IL-6 compared to those who survived at all-time points. CONCLUSION: The above findings suggest that doxycycline can provide a clinical benefit to dengue patients at high risk of complications. This effect could be mediated by decreasing pro-inflammatory cytokine levels.