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

OBJECTIVE: To 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 with betamethasone (BETA) and exogenous or endogenous interleukin-10 (IL-10). STUDY DESIGN: Macrophages were differentiated from cord blood monocytes (N=18). A serial dose-response (around 10(-8)M), in vitro study was used to examine the effect of DEX, BETA and IL-10, on proinflammatory (PI) cytokine release, phagocytosis and respiratory burst. RESULT: Exogenous IL-10 (10(-8)M) significantly (P \u3c 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 three agents at 10(-8)M on phagocytosis and respiratory burst. Inhibition of endogenous IL-10 with a monoclonal antibody significantly increased endotoxin-stimulated cytokine release by at least fourfold. CONCLUSION: Macrophages were relatively insensitive to therapeutic levels of DEX and BETA with regard to PI cytokine release. This study provides rationale for translational and preclinical research using airway instillation of IL-10 for the treatment of BPD