immunology of infectious and parasitic diseases - XXXVII Congress ...

STUDYING THE INFLAMMATORY RESPONSES TRIGGERED BY
STREPTOCOCCUS PNEUMONIAE INFECTION IN A MURINE MODEL –
EFFECTS OF A PDE4 INHIBITOR
LUCIANA PÁDUA TAVARES 1,2 , CRISTIANA COUTO GARCIA 1 , JULIANA
PRISCILA VAGO DA SILVA 2 , RAQUEL GREGORIO ARRIBADA 2 , MAURO
MARTINS TEIXEIRA 1 , LIRLÂNDIA PIRES SOUSA²
¹Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia,
ICB, UFMG
²Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia,
UFMG
Introduction and Objectives: Pneumonia, caused most frequently by
Streptococcus pneumoniae, is a major global health problem and is a leading
cause of morbidity and mortality worldwide, especially in developing countries.
The inflammatory response that follows microbial infections controls
dissemination of bacteria but may also cause tissue damage and mortality.
Drugs such as phosphodiesterase 4 (PDE4) inhibitors decrease inflammatory
responses effectively. Here, we describe the establishment of an animal model
of S. pneumoniae infection and evaluated whether the anti-inflammatory action
of PDE4 inhibitors interferes with the ability of the murine host to deal with
infection.Methods and Results: Male Balb/C mice were infected intranasally
with S. pneumoniae serotype 3 (ATCC 6303, 10 3 -10 6 CFU). Weight loss and
lethality were accompanied from the first day of infection (n=6 per group). There
was an inoculum-dependent death rate(10 6 and 10 5 CFU caused 100%, while
10 4 CFU caused 67% and 10 3 CFU 50% of lethality). Mice were infected with
10 5 CFU (100% lethality rate at day 4) and killed at 1, 2 or 3 days after infection.
Lung neutrophils (assessed by myeloperoxidase levels) and airway neutrophils
(recovered by bronchoalveolar lavage - BAL) peaked at 1 day after infection
and declined thereafter. Inflammatory mediators (TNF-α and CXCL1/KC),
phagocytosis and number of bacteria in BAL fluid had similar kinetics.
Treatment with Rolipram (ROL, 6 mg/kg, 1 h before infection) decreased
neutrophil recruitment in lungs, but not in BAL fluid, and decreased levels of
cytokines in BAL fluid at 24 h. Number of bacteria in BAL fluid were similar in
Rolipram and vehicle-treated animals. The percentage of leukocytes
phagocytosing bacteria was slightly greater in drug-treated animals.