C1 inhibitor treatment improves host defense in pneumococcal meningitis in rats and mice

Petra J G Zwijnenburg, Tom van der Poll, Sandrine Florquin, Machteld M J Polfliet, Timo K van den Berg, Christine D Dijkstra, John J Roord, C Erik Hack, A Marceline van Furth

Research output: Contribution to journalArticleAcademicpeer-review


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 languageEnglish
Pages (from-to)115-23
Number of pages9
JournalJournal of Infectious Diseases
Issue number1
Publication statusPublished - 1 Jul 2007

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