Development of Interleukin-12-Producing Capacity throughout Childhood

Upham, John W., Lee, Peter T., Holt, Barbara J., Heaton, Tricia, Prescott, Susan L., Sharp, Mary J., Sly, Peter D. and Holt, Patrick G. (2002) Development of Interleukin-12-Producing Capacity throughout Childhood. Infection and Immunity, 70 12: 6583-6588. doi:10.1128/IAI.70.12.6583-6588.2002

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Author Upham, John W.
Lee, Peter T.
Holt, Barbara J.
Heaton, Tricia
Prescott, Susan L.
Sharp, Mary J.
Sly, Peter D.
Holt, Patrick G.
Title Development of Interleukin-12-Producing Capacity throughout Childhood
Journal name Infection and Immunity
ISSN 1098-5522
Publication date 2002-12-01
Sub-type Article (original research)
DOI 10.1128/IAI.70.12.6583-6588.2002
Open Access Status File (Publisher version)
Volume 70
Issue 12
Start page 6583
End page 6588
Total pages 6
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
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.
Keyword Interleukin-12
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Journal note: Received 13 May 2002/Returned for modification 10 July 2002/Accepted 3 September 2002

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
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Created: Wed, 04 Mar 2009, 03:13:35 EST by Maria Campbell on behalf of School of Medicine