A model of
pneumococcal meningitis in young adult rats receiving
antibiotics once the
infection was established was developed. The intent was to mimic clinical and histopathological features of
pneumococcal meningitis in humans. The primary aim of the present study was to evaluate whether medical boosting of the peripheral neutrophil count affected the outcome of the
meningitis. The risk of terminal illness over the first 7 days after
infection was significantly reduced for rats who had elevated peripheral white blood cell counts after receiving
granulocyte-colony-stimulating factor (
G-CSF) prior to the
infection compared to that for untreated rats (P = 0.039 by the log rank test). The improved outcome was associated with reduced signs of cerebral cortical damage (P = 0.008). Furthermore, the beneficial effects of
G-CSF were associated with reduced bacterial loads in the cerebrospinal fluid (median, 1.1 x 10(5) versus 2.9 x 10(5) CFU/ml; P = 0.023) and in blood (median, 2.9 x 10(2) versus 6.3 x 10(2) CFU/ml; P = 0.024), as well as attenuated
pleocytosis (median, 800 x 10(6) versus 1,231 x 10(6) cells/liter; P = 0.025), 24 h after the
infection. Conversely, initiation of
G-CSF therapy 28 h postinfection did not alter the clinical or histological outcome relative to that for non-
G-CSF-treated rats. The magnitude of
bacteremia and pretreatment with
G-CSF were found to be prognostic factors for both outcome and brain damage. In summary, elevated neutrophil levels prior to the development of
meningitis result in reduced risks of death and brain damage. This beneficial effect is most likely achieved through improved control of the systemic disease.