C1 inhibitor treatment improves host defense in pneumococcal meningitis in rats and mice.
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.
Zwijnenburg
Petra J G
PJ
Department of Pediatrics, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. p.zwijnenburg@vumc.nl
van der Poll
Tom
T
Florquin
Sandrine
S
Polfliet
Machteld M J
MM
van den Berg
Timo K
TK
Dijkstra
Christine D
CD
Roord
John J
JJ
Hack
C Erik
CE
van Furth
A Marceline
AM
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
D018925:Chemokines; D003172:Complement C1; D050718:Complement C1 Inhibitor Protein; D016207:Cytokines; D016177:Macrophage-1 Antigen