Statins exert multiple effects besides lowering the serum
cholesterol level, which might be beneficial for patients with
sepsis and
infections. We designed this study to assess the therapeutic potential of
simvastatin in an established animal model of
pneumococcal meningitis, a disease characterized by high morbidity and mortality despite effective
antibiotic treatment. 24 h after injection of live pneumococci into the cisterna magna of mice, animals were clinically evaluated, cerebrospinal fluid (CSF) leukocyte counts and intracranial pressure were determined, and brains were removed for assessment of bacterial titer and blood-brain barrier breakdown. The following experimental groups were investigated: (I) no
infection and treatment with vehicle; (II)
infection and treatment with vehicle;
infection and treatment with (III) 20 mg/kg or (IV) 40 mg/kg
simvastatin s.c. 18 h before and just prior to
infection. Treatment with
simvastatin dose-dependently decreased CSF leukocyte counts, a marker for CNS
inflammation. In addition,
hypothermia was completely abolished in the 40 mg/kg
simvastatin group. In contrast, a neurological clinical score, and intracranial complications like increase in intracranial pressure and blood-brain barrier breakdown were not altered by the treatment. In conclusion,
simvastatin attenuates CNS leukocyte recruitment and systemic complications of
experimental pneumococcal meningitis.