Anti-inflammatory actions of endogenous and exogenous interleukin-10 versus glucocorticoids on macrophage functions of the newly born

Abstract

OBJECTIVETo determine whether specific macrophage immune functions of the newly born are insensitive to the actions of therapeutic levels of dexamethasone (DEX), previously measured in infants with bronchopulmonary dysplasia (BPD), compared to betamethasone (BETA) and exogenous or endogenous interleukin-10 (IL-10).STUDY DESIGNMacrophages were differentiated from cord blood monocytes (N=18). A serial dose response (around 10−8M), in vitro study was used to examine the effect of DEX, BETA and IL-10, on pro-inflammatory (PI) cytokine release, phagocytosis and respiratory burst.RESULTSExogenous IL-10 (10−8M) significantly (p<0.05) inhibited the endotoxin-stimulated release of IL-6, IL-8 and tumor necrosis factor by 63% to 82% with no significant effect by DEX and BETA. There was no inhibition by these 3 agents at 10−8M on phagocytosis and respiratory burst. Inhibition of endogenous IL-10 with a monoclonal antibody significantly raised endotoxin-stimulated cytokine release by at least 4 fold.CONCLUSIONMacrophages were relatively insensitive to therapeutic levels of DEX and BETA with regard to PI cytokine release. This study provides rationale for translational, preclinical research using airway instillation of IL-10 for the treatment of BPD.