title: Development of interleukin-12-producing capacity throughout childhood.
abstract: Increasing evidence indicates that the capacity to induce protective Th1 immune responses is impaired in early childhood, an observation that can be partially attributed to deficiencies in antigen-presenting-cell function. Synthesis of interleukin 12 (IL-12), a key Th1-trophic cytokine, is markedly reduced in the neonatal period, though there is a paucity of knowledge concerning the ontogeny of IL-12-synthetic capacity throughout the childhood years. Hence, we examined the production of bioactive IL-12 p70 by circulating mononuclear cells in a population of healthy individuals. As expected, the capacity to synthesize IL-12 p70 in response to either lipopolysaccharide or heat-killed Staphylococcus aureus was markedly impaired at birth, even after priming of cells with gamma interferon. Surprisingly however, IL-12 p70 synthesis by peripheral blood mononuclear cells from both 5- and 12-year-old children was still substantially below that seen in adults, and this did not appear to be related to excessive production of IL-10. In contrast, dendritic cells from adults and neonates, derived from monocytes with granulocyte-macrophage colony-stimulating factor and IL-4, synthesized equivalent amounts of IL-12 p70 in response to microbial stimulation. This indicates that the impaired capacity for IL-12 synthesis in childhood is not an intrinsic property of circulating mononuclear cells but rather can be readily overcome in response to appropriate maturational stimuli. Because IL-12 arose predominantly from circulating HLA-DR(+) cells that lacked B-cell- and monocyte-specific markers, we propose that the slow maturation of IL-12-synthetic capacity in the childhood years can be attributed to deficiencies in the number and/or function of dendritic cells.
authors.affiliation: Telethon Institute for Child Health Research and Centre for Child Health Research, Perth, Australia. johnu@ichr.uwa.edu.au
authors.forename: John W
authors.initials: JW
authors.lastname: Upham
authors.forename: Peter T
authors.initials: PT
authors.lastname: Lee
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Holt
authors.forename: Tricia
authors.initials: T
authors.lastname: Heaton
authors.forename: Susan L
authors.initials: SL
authors.lastname: Prescott
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Sharp
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
mesh_terms: D000328:Adult; D000375:Aging / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000276:immunology; D005312:Fetal Blood / Q000276:immunology*; D006358:Hot Temperature; D006801:Humans; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12