Cytokine responses correlate differentially with age in infancy and early childhood
Open accessAbstract
Summary: The functional differentiation of immune cells at early age plays a central role in immune physiology, e.g. for the sufficient eradication of pathogens. However, imbalances in effector cell responses may also have an impact in the pathophysiology of childhood diseases such as atopy and autoimmune disorders. As information on immune cell responses in infancy and early childhood is scarce, we conducted an observational, cross-sectional study in healthy newborns (n = 18), infants and young children (n = 54) aged 1–96 months and adult controls (n = 19) to assess cytokine mRNA and protein expression upon phorbol 12-myristate 13-actate/ionomycin stimulation and LPS-induced IL-12 expression in monocytes. The intracellular expression of interferon (IFN)-γ, tumour necrosis factor (TNF)-α (R = 0·748, P < 0·0001; R = 0·784, P < 0·0001, respectively) and interleukin (IL)-2 protein expression (R = 0·384, P = 0·008) was demonstrated to increase progressively with age. While a correlation between IL-4 protein expression and age was noted (R = 0·342, P = 0·007), the levels of IL-5 and IL-10 protein expression tended to be regulated on an individual basis during infancy and early childhood. An age correlation was also observed for intracellular IL-12 expression (R = 0·331, P = 0·009) in monocytes. These findings are valuable for further assessment of normal variations and maturation processes in immune cell responses and for the clinical–therapeutic monitoring of immunological status in various childhood diseases.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Innate immunity continues to mature through childhood.
“Innate immunity continues to mature through childhood, although few studies directly test this.”
From Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease (2017) · cites this paper as Härtel et al., 2005
IL-12 responses to bacterial challenge in monocytes are positively correlated with age from birth to age 8 years.
“Also, IL-12 responses to bacterial challenge in monocytes are positively correlated with age from birth to age 8 years (Härtel et al., 2005).”
From Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease (2017) · cites this paper as Härtel et al., 2005
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The expanding universe of T-cell subsets: Th1, Th2 and more
Mosmann, T. R., & Sad, S. (1996) · Immunology Today · doi:10.1016/0167-5699(96)80606-2 · Cited by 3,603 · see citing works
Acquisition of lymphokine-producing phenotype by CD4+ T cells
Seder, R. A., & Paul, W. E. (1994) · Annual Review of Immunology · doi:10.1146/annurev.iy.12.040194.003223 · Cited by 1,557 · see citing works
Lymphocyte subsets in healthy children from birth through 18 years of age
Shearer, W. T., Rosenblatt, H. M., Gelman, R. S., Oyomopito, R. A., Plaeger, S. F., Stiehm, E. R., Wara, D. W., Douglas, S. D., Luzuriaga, K., McFarland, E. J., et al. (2003) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2003.07.003 · Cited by 827 · see citing works
Regulation of cytokine signaling and inflammation
Hanada, T., & Yoshimura, A. (2002) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(02)00026-6 · Cited by 748 · see citing works
Immunophenotyping of blood lymphocytes in childhoodReference values for lymphocyte subpopulations
Comans-Bitter, W. M., de Groot, R., van den Beemd, R., et al. (1997) · The Journal of Pediatrics · doi:10.1016/s0022-3476(97)70200-2 · Cited by 741 · see citing works
Simultaneous quantitation of 15 cytokines using a multiplexed flow cytometric assay
Carson, R. T., & Vignali, D. A. A. (1999) · Journal of Immunological Methods · doi:10.1016/s0022-1759(99)00069-1 · Cited by 404 · see citing works
Romagnani, S. (1996) · Clinical Immunology and Immunopathology · doi:10.1006/clin.1996.0118 · Cited by 387 · see citing works
The paradigm of Th1 and Th2 cytokines
Singh, V. K., Mehrotra, S., & Agarwal, S. S. (1999) · Immunologic Research · doi:10.1007/bf02786470 · Cited by 318 · see citing works
T-cell function in newborn mice and humans
Adkins, B. (1999) · Immunology Today · doi:10.1016/s0167-5699(99)01473-5 · Cited by 316 · see citing works
Wilson, C. B., Westall, J., Johnston, L. A., et al. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112383 · Cited by 302 · see citing works
IL-10: a potential therapy for allergic inflammation?
Pretolani, M., & Goldman, M. (1997) · Immunology Today · doi:10.1016/s0167-5699(97)80023-0 · Cited by 160 · see citing works
Gasparoni, A., Ciardelli, L. M., Avanzini, A., Castellazzi, A. M., Carini, R., Rondini, G., & Chirico, G. (2003) · Neonatology · doi:10.1159/000073638 · Cited by 152 · see citing works
Immature anti-inflammatory response in neonates
SCHULTZ, C., Temming, P., Bucsky, P., Göpel, W., Strunk, T., & Härtel, C. (2003) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2004.02313.x · Cited by 146 · see citing works
Self-citationMaturation of human neonatal CD4+ and CD8+ T lymphocytes into Th1/Th2 effectors
Delespesse, G., Yang, L. P., Ohshima, Y., Demeure, C. E., Shu, U., Byun, D., & Sarfati, M. (1998) · Vaccine · doi:10.1016/s0264-410x(98)00101-7 · Cited by 142 · see citing works
Ex vivo induction of cytokine mRNA expression in human blood samples
Härtel, C., Bein, G., Müller‐Steinhardt, M., & Klüter, H. (2001) · Journal of Immunological Methods · doi:10.1016/s0022-1759(00)00334-3 · Cited by 118 · see citing works
Self-citationChipeta, J., Komada, Y., Zhang, X., Deguchi, T., Sugiyama, K., Azuma, E., & Sakurai, M. (1998) · Cellular Immunology · doi:10.1006/cimm.1998.1244 · Cited by 76 · see citing works
Ontogeny of T‐helper 1 and T‐helper 2 cytokine production in childhood
Smart, J. M., & Kemp, A. S. (2001) · Pediatric Allergy and Immunology · doi:10.1034/j.1399-3038.2001.012004181.x · Cited by 72 · see citing works
A Human Whole‐Blood Assay for Analysis of T‐Cell Function by Quantification of Cytokine mRNA
HÄRTEL, BEIN, KIRCHNER, et al. (1999) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.1999.00549.x · Cited by 55 · see citing works
The ontogeny of T lymphocyte maturation and function
Wilson, C. B. (1991) · The Journal of Pediatrics · doi:10.1016/s0022-3476(05)82182-1 · Cited by 51 · see citing works
Imbalanced Cytokine Secretion in Newborns
Kotiranta-Ainamo, A., Rautonen, J., & Rautonen, N. (2003) · Neonatology · doi:10.1159/000074959 · Cited by 42 · see citing works
Longitudinal study of intracellular T cell cytokine production in infants compared to adults
Buck, R. H., Cordle, C. T., Thomas, D., Winship, T. R., Schaller, J. P., & Dugle, J. E. (2002) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2002.01851.x · Cited by 40 · see citing works
Chipeta, J., Komada, Y., Zhang, X., et al. (2000) · Cellular Immunology · doi:10.1006/cimm.2000.1718 · Cited by 27 · see citing works
Schultz, C. (2003) · Methods in molecular biology · doi:10.1007/978-1-59259-345-3_4 · Cited by 14 · see citing works
Self-citationSchultz, C. (2003) · Humana Press eBooks · doi:10.1385/1-59259-345-3:29 · Cited by 8 · see citing works
Self-citationRegulation of Cytokine Signaling
Vuong, B. Q., McKeag, L., Losman, J. A., Li, J., Banks, A. S., Fay, S., Chen, P., & Rothman, P. B. (2005) · Humana Press eBooks · doi:10.1007/978-1-59259-909-7_11 · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- 4 Comans-Bitter WM, de Groot R, van den Beemd R et al. Immunophenotyping of blood lymphocytes in childhood. J Pediatr 1997; 130 :388-93.
Cited by
Sorted by citations
Kuhlman, K. R., Chiang, J. J., Horn, S., & Bower, J. E. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.05.020 · Cited by 208 · see citing works
Huggins, M. A., Sjaastad, F. V., Pierson, M., Kucaba, T. A., Swanson, W., Staley, C., Weingarden, A. R., Jensen, I. J., Danahy, D. B., Badovinac, V. P., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.07.028 · Cited by 114 · see citing works
Wang, P., You, D., Saravia, J., Shen, H., & Cormier, S. A. (2013) · Particle and Fibre Toxicology · doi:10.1186/1743-8977-10-29 · Cited by 58 · see citing works
- Authors
- Härtel, C., Adam, N., Strunk, T., Temming, P., Müller-Steinhardt, M., & Schultz, C.
- Affiliations
- University of Lübeck (DE)
- Institute for Immunology and Transfusion Medicine, University of Lübeck Medical School, Germany
- Corresponding author
- Härtel, C
- Venue
- Clinical and Experimental Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-09-11
- Volume
- 142
- Issue
- 3
- Pages
- 446-453
- ISSN
- 0009-9104 (ISSN-L)
- 1365-2249
- PMC
- PMC1809539
- OpenAlex
- W2128019577
- Cited by
- 143
- References
- 25
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 13 · 2016: 16 · 2015: 4 · 2014: 10 · 2013: 12 · 2012: 8
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical & Experimental Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universität zu Lübeck
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- cytokine expression, infancy, early childhood, neonates, monocytes, IL-12, interferon-gamma, TNF-α, interleukin-2, IL-4, IL-5, IL-10, lipopolysaccharide stimulation, immune cell differentiation
- MeSH terms
- Aging, Cell Differentiation, Child, Child, Preschool, Cross-Sectional Studies, Flow Cytometry, Humans, Infant, Infant, Newborn, Interferon-gamma, Interleukin-2, Lipopolysaccharides, Monocytes, RNA, Messenger, T-Lymphocytes, Tumor Necrosis Factor-alpha, Interleukin-4, Interleukin-5, Cytokines, Interleukin-10, Interleukin-12
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
