IL-1beta induces an exaggerated pro- and anti-inflammatory response in peritoneal macrophages of children compared with adults.

Abstract

Children have a lower incidence of acute lung injury (ALI) compared with adults. Because ALI appears to be the end result of systemic hyperinflammation, children may either have 1) an attenuated pro-inflammatory response or 2) an augmented anti-inflammatory response compared with adults. The purpose of this study was to determine the IL-1-induced pro- and anti-inflammatory response of pediatric vs. adult peritoneal macrophages (PMs). We hypothesized that pediatric PMs would have an enhanced anti-inflammatory response compared with adult PMs. Human PMs were collected during elective laparoscopic procedures, cultured, and stimulated with IL-1beta. IL-6, IL-8, IL-10, and TNFalpha production were determined by ELISA. Statistical analyses were by ANOVA; a P <0.05 was significant. Our results showed that IL-1beta induced an 11-fold increase in IL-10 production in pediatric PMs (659+/-103 vs. 60+/-25 control, P <0.05). There was no IL-10 production in IL-1beta-stimulated adult PMs. IL-1beta-induced TNF production was greater in children compared with adults (2152+/-166 vs. 592+/-188, P <0.05). Similarly, IL-1beta-induced IL-6 production was greater in pediatric PMs compared with adults (532+/-3 vs. 444+/-52, P <0.05). There was no difference in IL-1beta-induced IL-8 production in children compared with adults. The IL-10:TNFalpha ratio after IL-1beta stimulation was 0.306+/-0.056 in pediatric macrophages and 0.020+/-0.015 in adult macrophages ( P<0.01). In conclusion, IL-1beta-induced IL-6 and TNFalpha production were greater in pediatric than adult PMs. Furthermore, pediatric PMs had an 11-fold increase in IL-1beta-induced IL-10 production, while adult PMs did not produce IL-10. Therefore, IL-1beta induces both a pro- and an anti-inflammatory response in pediatric PMs, whereas adult PMs produce only pro-inflammatory cytokines in response to IL-1beta. The exaggerated anti-inflammatory IL-10 response in children may be an important factor in the observed differences in ALI between children and adults.