TY - JOUR
T1 - Modulation of inflammation and cachectin activity in relation to treatment of experimental hemophilus influenzae type b meningitis
AU - Mustafa, M. M.
AU - Ramilo, O.
AU - Mertsola, J.
AU - Risser, R. C.
AU - Beutler, B.
AU - Hansen, E. J.
AU - McCracken, G. H.
N1 - Funding Information:
This work was supported by grant HD-22766 from the National Institute of Child Health and Human Development. J. M. was partially supported by a grant from the Academy of Finland.
PY - 1989/11
Y1 - 1989/11
N2 - By use of an experimental lapin model, the effect of ceftriaxone therapy on inflammation during Hemophilus influenzae type b (Hib) meningitis was evaluated. Meningitis was induced by intracisternal inoculation of 2 x 104 to 2 x 105 colony-forming units of Hib. Administration of ceftriaxone 6 h after infection provoked rapid bacterial lysis associated with greatly increased concentrations of bacteria-free endotoxin (lipooligosaccharide) and tumor necrosis factor a (TNF) in the cerebrospinal fluid (CSF). CSF TNF activity peaked 2 h after initiation of antibiotic therapy (24.4 ± 2 ng/ml), was significantly higher than that in untreated controls (1.4 ± 1.1 ng/ml; P.05), and was associated with a substantially increased inflammatory response as reflected by higher CSF white blood cell count (24, 500 ± 8, 151 vs. 1, 920 ± 644 in untreated controls; P.05), lower glucose, and higher protein and lactate concentrations. Simultaneous administration of dexamethasone with antibiotic therapy resulted in a significant reduction in CSF TNF activity that was associated with a substantial reduction in CSF white blood cell count. These data suggest that initiation of ceftriaxone therapy in experimental Hib meningitis exacerbates the meningeal inflammatory response, which can be modulated by concurrent dexamethasone administration.
AB - By use of an experimental lapin model, the effect of ceftriaxone therapy on inflammation during Hemophilus influenzae type b (Hib) meningitis was evaluated. Meningitis was induced by intracisternal inoculation of 2 x 104 to 2 x 105 colony-forming units of Hib. Administration of ceftriaxone 6 h after infection provoked rapid bacterial lysis associated with greatly increased concentrations of bacteria-free endotoxin (lipooligosaccharide) and tumor necrosis factor a (TNF) in the cerebrospinal fluid (CSF). CSF TNF activity peaked 2 h after initiation of antibiotic therapy (24.4 ± 2 ng/ml), was significantly higher than that in untreated controls (1.4 ± 1.1 ng/ml; P.05), and was associated with a substantially increased inflammatory response as reflected by higher CSF white blood cell count (24, 500 ± 8, 151 vs. 1, 920 ± 644 in untreated controls; P.05), lower glucose, and higher protein and lactate concentrations. Simultaneous administration of dexamethasone with antibiotic therapy resulted in a significant reduction in CSF TNF activity that was associated with a substantial reduction in CSF white blood cell count. These data suggest that initiation of ceftriaxone therapy in experimental Hib meningitis exacerbates the meningeal inflammatory response, which can be modulated by concurrent dexamethasone administration.
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U2 - 10.1093/infdis/160.5.818
DO - 10.1093/infdis/160.5.818
M3 - Article
C2 - 2809257
AN - SCOPUS:0024441126
SN - 0022-1899
VL - 160
SP - 818
EP - 825
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 5
ER -