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Inflammatory signatures and immunomodulation in neonates: a pilot study.

Title: Inflammatory signatures and immunomodulation in neonates: a pilot study.
Authors: Leonardi, L.; Pennetta, V.; Laitano, R.; Carsetti, R.; Duse, M.; Fiore, M.; Natale, F.; Tarani, L.; Spalice, A.; Förster-Waldl, E.
Source: Clinica Terapeutica; May/Jun2025, Vol. 176 Issue 3, p350-357, 8p
Subject Terms: AGE groups; CORD blood; TOLL-like receptors; NEONATAL diseases; INFLAMMATION
Abstract: Background. The precise diagnosis of inflammatory responses is essential for managing infectious diseases. Dysregulated inflammatory responses can lead to death and high morbidity in some subjects due to sensitive age, genetic predisposition, or other comorbidities. More specifically, dysregulated immunological development in newborns has been investigated to elucidate inflammatory regulation in prone populations, as being the first step to future immunomodulatory therapeutic interventions. Indeed, compared to adults, neonates display both an immature immune response to microorganisms, due to a diminished Th1 response and an immature compensatory anti-inflammatory response. Methods. In this exploratory study, we aimed to characterize inflammatory signatures in i) preterm newborns, ii) full-term newborns, iii) fullterm newborns exposed in-utero to Cytomegalovirus (CMV) infections, and iv) healthy adults as a further control group. Our investigation used a whole-blood approach to quantify the basal and the Toll-like receptors (TLRs)-induced cytokine responses. Samples from cord blood and peripheral blood (of healthy adults) were stimulated or not with ligands for TLR1/2, TLR4, and TLR7/8 to elicit cytokine production. Results. We found that after TLR7/8 stimulation the blood of full-term newborns showed higher concentrations of IL-6 and TNF-α compared to the other groups. Moreover TLR7/8 ligand, compared to other TLR ligands, potentiated pro-inflammatory responses according to the presence of IL-6, TNF-α and CXCL8 in adults, while in preterm newborns we disclosed TNF-α α elevation. In preterm newborns, we also observed increased TLR1/2-induced IL-10 concentration suggestive of modifications in the immunosuppressive and inflammatory state. Conclusions. Our pilot results strongly encourage further investigations comparing age groups and different immunomodulatory agents further promoting the discussion that TLR7/8 ligands could be suitable vaccine adjuvant candidates for newborns. At the same time, IL-10-associated immunomodulation (monoclonal antibody anti-IL10, anti-IL-10 receptors, or anti-TLR1/2) might be a future therapeutic option for cases of overwhelming neonatal inflammatory diseases. [ABSTRACT FROM AUTHOR]
: Copyright of Clinica Terapeutica is the property of Societa Editrice Universo s.r.l. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Complementary Index