| Área: Micobacteriologa ( Divisão C )
DIFERRENTIAL MEDIATION OF NEUTROPHIL ACCUMULATION INDUCED BY BCG IN MOUSE PLEURISY
Andre Luis Peixoto Candéa (Fiocruz); Octávio Menezes de Lima Jr (Fiocruz); Elaine Cruz Rosas (Fiocruz); Maria das Graças Muller de Oliveira Henriques (Fiocruz)
Resumo
Introduction: Mycobacterial infections are among the main health problems worldwide. However, the initial inflammatory events during pulmonary mycobacterial infection are still unclear. There are increasing evidences that neutrophils are important in the control of mycobacterial infections, but few studies focused on the investigation of the inflammatory mediators and cytokines involved in mycobacteria-induced neutrophilia. In the present study we performed a pharmacological characterization of several mediators on the leukocyte influx in a murine model of Mycobacterium Bovis-BCG-induced pleurisy, analyzing three different time points of the reaction.
Methods and Results: Male C57Bl/6 mice were injected with Mycobacterium bovis-BCG (4 x 105 CFU/cavity) diluted in 100 mL of sterile saline. After 4 h, 24 h or 15 days the mice were sacrificed by CO2 inhalation and the thoracic cavity was washed with 1 mL of heparinized PBS, to analyze total and differential leukocyte accumulation. Drug pretreatments with: WEB 2170 (2-4 mg kg-1, i.p.), diacerein (30-100 mg kg-1, p.o.), CP-105696 (1-4 mg kg-1, i.p.) L-NAME (5-25 mg kg-1, i.p.) or thalidomide (6-30 mg kg-1, s.c.) were performed 1h before and, in some groups, 13 and 14 days after BCG administration. All procedures were approved by the Committee for Animal Care and Use (CEUA-FIOCRUZ) under L0052-2008 license. After 4 h only the PAF antagonist WEB2170 inhibited neutrophil accumulation. The 24 h neutrophilia was inhibited by the LTB4 antagonist CP-105696, the NO inhibitor L-NAME, the TNFá inhibitor thalidomide and the IL-1 inhibitor diacerein. After 15 days only L-NAME failed to inhibit neutrophil accumulation.
Conclusion: Our data indicate that BCG-induced neutrophil accumulation is differentially mediated along the several phases of the inflammatory reaction.
Palavras-chave: Micobacterium bovis, tuberculose, bcg, inflamação, neutrófilos |