Cytokine responses correlate differentially with age in infancy and early childhood

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.

[1]  Alexander S. Banks,et al.  Regulation of Cytokine Signaling , 2005 .

[2]  J. Rautonen,et al.  Imbalanced Cytokine Secretion in Newborns , 2004, Neonatology.

[3]  W. Göpel,et al.  Immature anti‐inflammatory response in neonates , 2004, Clinical and experimental immunology.

[4]  R. Gelman,et al.  Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. , 2003, The Journal of allergy and clinical immunology.

[5]  R. Carini,et al.  Age-Related Changes in Intracellular Th1/Th2 Cytokine Production, Immunoproliferative T Lymphocyte Response and Natural Killer Cell Activity in Newborns, Children and Adults , 2003, Neonatology.

[6]  W. Kiess,et al.  Cytokines and colony stimulating factors : methods and protocols , 2003 .

[7]  C. Schultz Intracytoplasmic detection of proinflammatory cytokines and chemokines in monocytes by flow cytometry. , 2003, Methods in molecular biology.

[8]  A. Yoshimura,et al.  Regulation of cytokine signaling and inflammation. , 2002, Cytokine & growth factor reviews.

[9]  R. Buck,et al.  Longitudinal study of intracellular T cell cytokine production in infants compared to adults , 2002, Clinical and experimental immunology.

[10]  Joanne M. Smart,et al.  Ontogeny of T‐helper 1 and T‐helper 2 cytokine production in childhood , 2001, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[11]  G. Bein,et al.  Ex vivo induction of cytokine mRNA expression in human blood samples. , 2001, Journal of immunological methods.

[12]  H. Yamamoto,et al.  Neonatal (cord blood) T cells can competently raise type 1 and 2 immune responses upon polyclonal activation. , 2000, Cellular immunology.

[13]  V. Singh,et al.  The paradigm of Th1 and Th2 cytokines , 1999, Immunologic research.

[14]  D. Vignali,et al.  Simultaneous quantitation of 15 cytokines using a multiplexed flow cytometric assay. , 1999, Journal of immunological methods.

[15]  B. Adkins T-cell function in newborn mice and humans. , 1999, Immunology today.

[16]  Kirchner,et al.  A Human Whole‐Blood Assay for Analysis of T‐Cell Function by Quantification of Cytokine mRNA , 1999, Scandinavian journal of immunology.

[17]  G. Delespesse,et al.  Maturation of human neonatal CD4+ and CD8+ T lymphocytes into Th1/Th2 effectors. , 1998, Vaccine.

[18]  J. Chipeta,et al.  CD4+ and CD8+ cell cytokine profiles in neonates, older children, and adults: increasing T helper type 1 and T cytotoxic type 1 cell populations with age. , 1998, Cellular immunology.

[19]  M. Goldman,et al.  IL-10: a potential therapy for allergic inflammation? , 1997, Immunology today.

[20]  R de Groot,et al.  Immunophenotyping of blood lymphocytes in childhood. Reference values for lymphocyte subpopulations. , 1997, The Journal of pediatrics.

[21]  S. Romagnani Th1 and Th2 in human diseases. , 1996, Clinical immunology and immunopathology.

[22]  T. Mosmann,et al.  The expanding universe of T-cell subsets: Th1, Th2 and more. , 1996, Immunology today.

[23]  R. Seder Acquisition of lymphokine-producing phenotype by CD4+ T cells. , 1994, The Journal of allergy and clinical immunology.

[24]  W. Paul,et al.  Acquisition of lymphokine-producing phenotype by CD4+ T cells. , 1994, Annual review of immunology.

[25]  C. Wilson,et al.  The ontogeny of T lymphocyte maturation and function. , 1991, The Journal of pediatrics.

[26]  D. Lewis,et al.  Decreased production of interferon-gamma by human neonatal cells. Intrinsic and regulatory deficiencies. , 1986, The Journal of clinical investigation.