Dexamethasone Improves Neutrophil Mediated Killing of Group B streptococcus(GBS) † 1463

Abstract

Previous reports about the effect of corticosteroids on neutrophil phagocytic-killing function are conflicting. GBS is a significant cause of infection in certain adult population and neonates. Neutrophil mediated bacterial killing is an important defense against GBS infection. We hypothesized that dexamethasone (DEX) would affect neutrophil mediated bacterial killing and studied this in vitro. Neutrophils (PMNs) were isolated from healthy adults (n=27) and term neonates (n=8) by dextran and ficoll-hypaque density centrifugation and resuspended to a concentration of 2.5 × 107 cells/ml. PMNs were then either: a) incubated for two hours with various concentrations (0 to 100 mcg/ml) of DEX in the presence of GBS (0.5 × 105 cfu/ml, serotype III, strain SS 878), complement, and human antibody; or b) incubated with the same concentrations of dexamethasone for one hour, washed and resuspended to the same above PMNs concentration then incubated for two hours with GBS, complement, and human antibody. In both intances,bacterial killing was calculated based on colony counts performed prior to and after the final two hour incubation. No bacterial killing was noted in negative controls. Results are expressed as the log antibody-1 level (log Ab-1) at which the largest reciprocal dilution promoted ≥ 90% bacterial killing. Adult PMNs that were exposed to DEX during their interaction with GBS had no change in killing activity. However, adult PMNs exposed to the same concentrations of DEXbefore their interaction to GBS demonstrated a significant increase in killing activity (log Ab-1 = 1.24 at 100 mcg/ml vs. 0.8 at zero mcg/ml). Neonatal PMNs exposed to DEX during their interaction to GBS had a significant decrease in their killing activity (log Ab-1= 1.0 at zero mcg/ml vs. 0.45 at 100 mcg/ml). Interestingly, neonatal PMNs that were exposed to DEX before their interaction to GBS tended to improve their killing activity, though this was not statistically significant. Adult and neonatal PMNs enhance their killing activity, in a dose response fashion, when they are exposed to DEX only prior to their interaction with GBS. However, neonatal PMNs exposed to DEX only at the time of their encounter with GBS will demonstrate, in a dose response fashion, a decreased killing activity against these bacteria. The interaction of DEX, PMNs and GBS is complex and we speculate it may depend upon the timing of these interactions, the population of PMNs and the concentration of DEX.