Abstract
In spite of antibiotic treatment, pneumococcal meningitis continues to be associated with significant morbidity and mortality. The complement system is a key component of innate immunity against invading pathogens. However, activation of complement is also involved in tissue damage, and complement inhibition by C1 inhibitor (C1-inh) is beneficial in animal models of endotoxemia and sepsis. In the present study, we demonstrate classical pathway complement activation during pneumococcal meningitis in rats. We also evaluate the effect of C1-inh treatment on clinical illness, bacterial clearance, and inflammatory responses in rats and mice with pneumococcal meningitis. C1-inh treatment was associated with reduced clinical illness, a less-pronounced inflammatory infiltrate around the meninges, and lower brain levels of proinflammatory cytokines and chemokines. C1-inh treatment increased bacterial clearance, possibly through an up-regulation of CR3. Hence, C1-inh may be a useful agent in the treatment of pneumococcal meningitis
Original language | English |
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Pages (from-to) | 115-123 |
Number of pages | 9 |
Journal | Journal of infectious diseases |
Volume | 196 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Jul 2007 |
Keywords
- Animals
- Brain Chemistry
- Brain/immunology
- Cerebrospinal Fluid/microbiology
- Chemokines/analysis
- Colony Count, Microbial
- Complement Activation
- Complement C1 Inhibitor Protein/administration & dosage
- Complement C1/antagonists & inhibitors
- Complement Pathway, Classical
- Cytokines/analysis
- Disease Models, Animal
- Humans
- Macrophage-1 Antigen/biosynthesis
- Male
- Meninges/pathology
- Meningitis, Pneumococcal/immunology
- Mice
- Mice, Inbred C57BL
- Rats
- Rats, Wistar
- Streptococcus pneumoniae/isolation & purification