TBXA2 PLAYS AN IMPORTANT ROLE IN THE VASCULAR AND INFLAMMATORY ALTERATIONS INDUCED BY DV INFECTION.

Daniel Cisalpino (UFMG); Caio Fagundes (UFMG); Rodrigo Guabiraba (UFMG); Flávio Amaral (UFMG); Rafael Souza (UFMG); Lirlândia Sousa (UFMG); Mauro Teixeira (UFMG); Danielle Souza (UFMG)

Introduction: Dengue virus (DV) has emerged as the most relevant arthropod-borne virus in tropical areas. During the infection, it is observed increase in the vascular permeability, haemoconcentration and thrombocytopenia. Eicosanoids are a major class of lipid mediators involved in several homeostatic and inflammatory processes. Our group is evaluating the importance of Thromboxane A₂ (TBXA₂) and its receptors in an experimental model of Dengue virus serotype 2 (DEN-2) infection. Methods: Balb/c mice were infected intra-peritoneally with 1 PFU of DEN-2, and, from the 5^th day of infection, received the following treatments: Acetyl Salicylic Acid (AAS) (dose of 100, 10 and 1 mg/kg), BMS 180291 (20mg/kg, antagonist for Thromboxane receptors) and Indomethacin (INDO) (2mg/kg). Non-infected mice, and animals treated only with drug vehicle were used as controls. After infection, lethality rates, hematocrit levels and platelet number, viral titers, cytokine production and neutrophil influx were evaluated. Results and Discussion: Treated animals showed an improved clinical condition as indicated by reduced hematocrit and higher platelet count. Inflammatory parameters, such as production of cytokines in the liver, in the spleen and in the lungs and MPO activity in these organs, were also significantly decreased in the treated groups. The observed effects were dose dependent for AAS, and the 100mg/kg-treated group presented similar results to that found in BMS treated animals. This suggests that the reduced inflammatory response in the treated groups studied were due to blockade of TBXA₂ action. However, none of the treated groups showed smaller lethality rates that vehicle-treated ones, probably to high viral loads found after infection. Conclusion: TBXA₂ plays a significant role in the characteristic inflammatory alterations induced by DV infection, and its blockade results in reduced inflammatory response after disease onset. However, TBXA₂ inhibition does not interfere in host ability to control the infection.

Financial Support: CNPq, FAPEMIG