Glucocorticoids are widely used in children as anti-inflammatory and cytoxic agents, controversially in acute respiratory distress syndrome and shock states. Their anti-inflammatory mechansim of action and the associated risk of infection is thought to be possibly secondary to PMN dysfunction. We comprehensively evaluated three anti-inflanmatory glucocorticoids with differing potencies, investigating the effect and the dose response of HC, MP and DXM on in vitro hunan PMN function. PMNs were isolated to greater than 90% purity from peripheral blood layered on a dextran/ficoll-hypaque gradient. The cells were tested for FMLP(N-Formyl-l-methionyl-1-leucyl-1-phenylalanine) stimulated aggregation after incubation(60 min.)with HC, MP and DXM,- CytoB/FMLP stimulated superoxide production and chemotaxic activity using the GAllin modification of the Boyden chamber technique with Cr51 PMNs stimulated by E.Coli endotoxin. PMN aggregation was significantly inhibited by all concentrations of HC, the least potent of the anti-inflanmatory steroids and only by moderate and high concentrations of hP and DXM.
Similar suppression of PMN superoxide and chemotaxis by HC was found at the highest concentration of 8×10−3 M (Cont.220±36 vs HC 17.6±11.4 nmoles/10 cells p<.001 and Cont. 22.4±3.87. vs HC 10.8±1.4% p<.004 respectively). Further studies of PMN bacterial killing and degranulation in vitro are in progress to be followed by in vivo studies using pharmacological doses.
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Hodder, F., Vandeven, C., Wong, C. et al. 987 HYDROCORTISONE (HC) INDUCED GREATER IN VITRO SUPPRESSION OF HUMAN POLYMORPHONUCLEAR GRANULOCYTE (PMN) AGGREGATION, AND OTHER PMN FUNCTION METHLPREDNISOLONE (MP) AND DEXAMETHASONE (DXM). Pediatr Res 19, 275 (1985) doi:10.1203/00006450-198504000-01017