Protective role of NF-kappaB1 (p50) in experimental pneumococcal meningitis.
Nuclear factor-kappaB (NF-kappaB) is a critical regulator of many genes involved in the pathogenesis of bacterial meningitis. Recently, activation of NF-kappaB was shown to be a key event in the inflammatory host response and the development of intracranial complications during experimental pneumococcal meningitis. Since the p50 subunit of NF-kappaB lacks a transactivation domain and can therefore act as a transcriptional repressor, we investigated whether NF-kappaB1 (p50) exerts anti-inflammatory effects in pneumococcal meningitis. p50-deficient mice had higher cerebellar pneumococcal titers (10.06+/-0.47 vs. 8.51+/-1.06 log colony-forming units [cfu]/cerebellum), cerebrospinal fluid (CSF) leukocyte counts (11,475+/-2340 vs. 8444+/-1405 cells/microl) and brain concentrations of interleukin-1beta (125.9+/-50.3 vs. 58.5+/-52.2 pg/mg protein) than their wild-type littermates. With ceftriaxone therapy, none of the wild-type mice but 43% of the p50-deficient animals died. In conclusion, lack of NF-kappaB1 (p50) was associated with impaired bacterial clearing, enhanced inflammatory host response and increased mortality during pneumococcal meningitis.
Kastenbauer
Stefan
S
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, 81377 Munich, Germany. stefan@kastenbauer.de
Koedel
Uwe
U
Weih
Falk
F
Ziegler-Heitbrock
Löms
L
Pfister
Hans-Walter
HW
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D002531:Cerebellum / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000378:metabolism; D007958:Leukocyte Count; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000382:microbiology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D013296:Streptococcus pneumoniae / Q000254:growth & development; D051996:Transcription Factor RelA
D007375:Interleukin-1; D016328:NF-kappa B; D051996:Transcription Factor RelA