title: Dengue Patients Treated with Doxycycline Showed Lower Mortality Associated to a Reduction in IL-6 and TNF Levels.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Terry M
authors: TM
authors: Fredeking
authors: Jorge E
authors: JE
authors: Zavala-Castro
authors: Pedro
authors: P
authors: González-Martínez
authors: William
authors: W
authors: Moguel-Rodríguez
authors: Ernesto C
authors: EC
authors: Sanchez
authors: Michael J
authors: MJ
authors: Foster
authors: Departamento de Epidemiologia, Faculdade de Saude Publica da Universidade de Sao Paulo, Av. Dr. Arnaldo, 715, Cerqueira Cesar, CEP 01246-904, Sao Paulo, SP, Brazil. frediazq@msn.com.
authors: Fredi A
authors: FA
authors: Diaz-Quijano
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D015536:Down-Regulation; D004318:Doxycycline / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D008800:Mexico; D016016:Proportional Hazards Models; D012307:Risk Factors; D019595:Severe Dengue / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D000890:Anti-Infective Agents; D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D004318:Doxycycline