Mohamed Jeljeli1,2, Valérie Guérin-El Khourouj1,2, Béatrice Pédron1,2, Pierre Gressens2,3, Olivier Sibony2,4, Ghislaine Sterkers5,6. 1. Laboratory of Immunology, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris AP-HP, 75019, Paris, France. 2. Univ. Paris Diderot, Sorbonne Paris Cité, Paris, France. 3. INSERM UMR1141, Paris, France. 4. Department of Gynecology Obstetric, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris AP-HP, 75019, Paris, France. 5. Laboratory of Immunology, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris AP-HP, 75019, Paris, France. ghislaine.sterkers@aphp.fr. 6. Univ. Paris Diderot, Sorbonne Paris Cité, Paris, France. ghislaine.sterkers@aphp.fr.
Abstract
BACKGROUND: Altered production of cytokines is believed to contribute to early childhood susceptibility to infection. The aim of this study was to get further insight into the developmental patterns of cytokine responses from birth to adulthood. METHODS: The expression levels of 13 cytokines were compared in the supernatants of phytohemaggluttinin (PHA)-stimulated whole blood from healthy neonates (cord blood, n = 8), infants ( < 1-year-old, n = 20), and school-aged children (3-15 y; n = 20). Five adults were used as reference. RESULTS: While Th1, Th2, and Th17 cytokine levels increased progressively from birth to childhood (Mann-Whitney, p < 0.003), high IL-10 secretion at birth dropped to low adult levels in infants (p < 0.004) such that a negative correlation between IL-10 and Th1, Th2, and Th17 cytokine levels at birth (Spearman's correlation, r < -0.70, p < 0.01) converted to a positive correlation in infants (r > 0.60, p < 0.001). Finally, high IL-2, IL-7, and Granulocyte-Colony Stimulating factor (G-CSF) cytokine levels at birth decreased steadily over the first year of life (Mann-Whitney, p ≤ 0.001). CONCLUSION: The most noticeable result of the study is the rapid shift from enhanced IL-10 secretion capacity at birth toward balanced IL-10/Th1/Th2/Th17 cytokine levels early in life. This change appears an essential precondition to fight pathogens and at the same time to avoid overwhelming inflammatory reactions.
BACKGROUND: Altered production of cytokines is believed to contribute to early childhood susceptibility to infection. The aim of this study was to get further insight into the developmental patterns of cytokine responses from birth to adulthood. METHODS: The expression levels of 13 cytokines were compared in the supernatants of phytohemaggluttinin (PHA)-stimulated whole blood from healthy neonates (cord blood, n = 8), infants ( < 1-year-old, n = 20), and school-aged children (3-15 y; n = 20). Five adults were used as reference. RESULTS: While Th1, Th2, and Th17 cytokine levels increased progressively from birth to childhood (Mann-Whitney, p < 0.003), high IL-10 secretion at birth dropped to low adult levels in infants (p < 0.004) such that a negative correlation between IL-10 and Th1, Th2, and Th17 cytokine levels at birth (Spearman's correlation, r < -0.70, p < 0.01) converted to a positive correlation in infants (r > 0.60, p < 0.001). Finally, high IL-2, IL-7, and Granulocyte-Colony Stimulating factor (G-CSF) cytokine levels at birth decreased steadily over the first year of life (Mann-Whitney, p ≤ 0.001). CONCLUSION: The most noticeable result of the study is the rapid shift from enhanced IL-10 secretion capacity at birth toward balanced IL-10/Th1/Th2/Th17 cytokine levels early in life. This change appears an essential precondition to fight pathogens and at the same time to avoid overwhelming inflammatory reactions.
Authors: Kinga K Smolen; Alec L Plotkin; Casey P Shannon; Olubukola T Idoko; Jensen Pak; Alansana Darboe; Simon van Haren; Nelly Amenyogbe; Scott J Tebbutt; Tobias R Kollmann; Beate Kampmann; Al Ozonoff; Ofer Levy; Oludare A Odumade Journal: Cytokine Date: 2021-09-28 Impact factor: 3.861