title: 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.
authors.affiliation: Division of Pediatric Surgery and GI, Tumor and Endocrine Surgery, Dept. of Surgery, University of Colorado Health Sciences Center and The Children's Hospital, 4200 East Ninth Ave., Box C320, Denver, CO 80262, USA. Katherine.Barsness@uchsc.edu
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Barsness
authors.forename: Denis D
authors.initials: DD
authors.lastname: Bensard
authors.forename: David A
authors.initials: DA
authors.lastname: Partrick
authors.forename: Casey M
authors.initials: CM
authors.lastname: Calkins
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hendrickson
authors.forename: Anirban
authors.initials: A
authors.lastname: Banerjee
authors.forename: Robert C
authors.initials: RC
authors.lastname: McIntyre
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008875:Middle Aged; D012128:Respiratory Distress Syndrome / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10