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.