C1 Inhibitor Treatment Improves Host Defense in Pneumococcal Meningitis in Rats and Mice

• Published in: The Journal of infectious diseases Vol. 196; no. 1; pp. 115 - 123
• Main Authors: Zwijnenburg, Petra J. G., Poll, Tom van der, Florquin, Sandrine, Polfliet, Machteld M. J., van den Berg, Timo K., Dijkstra, Christine D., Roord, John J., Erik Hack, C., Marceline van Furth, A.
• Format: Journal Article
• Language: English
• Published: United States The University of Chicago Press 01.07.2007; University of Chicago Press
• Subjects: Animal models; Animals; Bacteria; Bacterial meningitis; Blood; Brain - immunology; Brain - pathology; Brain Chemistry; Central nervous system; Cerebrospinal fluid; Cerebrospinal Fluid - microbiology; Chemokines - analysis; Colony Count, Microbial; Complement Activation; Complement C1 - antagonists & inhibitors; Complement C1 Inhibitor Protein - administration & dosage; Complement C1 Inhibitor Protein - pharmacology; Complement Pathway, Classical; Cytokines; Cytokines - analysis; Disease Models, Animal; Humans; Inoculation; Leukocytes; Macrophage-1 Antigen - biosynthesis; Male; Meninges - pathology; Meningitis, Pneumococcal - immunology; Meningitis, Pneumococcal - microbiology; Meningitis, Pneumococcal - pathology; Mice; Mice, Inbred C57BL; Pneumococcal meningitis; Rats; Rats, Wistar; Streptococcus pneumoniae; Streptococcus pneumoniae - isolation & purification
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/518609

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 lesspronounced 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.