Simvastatin attenuates leukocyte recruitment in experimental bacterial meningitis.

Abstract

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.