title: C1 inhibitor treatment improves host defense in pneumococcal meningitis in rats and mice.
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.
authors.affiliation: Department of Pediatrics, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. p.zwijnenburg@vumc.nl
authors.forename: Petra J G
authors.initials: PJ
authors.lastname: Zwijnenburg
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Machteld M J
authors.initials: MM
authors.lastname: Polfliet
authors.forename: Timo K
authors.initials: TK
authors.lastname: van den Berg
authors.forename: Christine D
authors.initials: CD
authors.lastname: Dijkstra
authors.forename: John J
authors.initials: JJ
authors.lastname: Roord
authors.forename: C Erik
authors.initials: CE
authors.lastname: Hack
authors.forename: A Marceline
authors.initials: AM
authors.lastname: van Furth
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D001923:Brain Chemistry; D002555:Cerebrospinal Fluid / Q000382:microbiology; D018925:Chemokines / Q000032:analysis; D015169:Colony Count, Microbial; D003167:Complement Activation; D003172:Complement C1 / Q000037:antagonists & inhibitors*; D050718:Complement C1 Inhibitor Protein / Q000008:administration & dosage / Q000494:pharmacology*; D003171:Complement Pathway, Classical; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D006801:Humans; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008297:Male; D008578:Meninges / Q000473:pathology; D008586:Meningitis, Pneumococcal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017208:Rats, Wistar; D013296:Streptococcus pneumoniae / Q000302:isolation & purification
chemical_list: D018925:Chemokines; D003172:Complement C1; D050718:Complement C1 Inhibitor Protein; D016207:Cytokines; D016177:Macrophage-1 Antigen