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Published on: August 7, 2017
Inflammatory signatures and immunomodulation in neonates: a pilot study
L Leonardi1, V Pennetta1, R Laitano2
1Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Rome, Italy.
Insights
Newborns exhibit distinct inflammatory responses compared to adults. Full-term newborns showed heightened IL-6 and TNF-α after TLR7/8 stimulation, suggesting potential vaccine adjuvant applications.
Area of Science:
- Immunology
- Neonatal Health
- Infectious Disease Management
Background:
- Precise diagnosis of inflammatory responses is crucial for managing infectious diseases.
- Dysregulated inflammation in neonates, particularly newborns, presents unique challenges due to immature immune systems.
- Understanding neonatal immune responses is key to developing future immunomodulatory therapies.
Purpose of the Study:
- To characterize inflammatory signatures in preterm newborns, full-term newborns, and healthy adults.
- To compare basal and Toll-like receptor (TLR)-induced cytokine responses across these groups.
- To investigate the impact of in-utero Cytomegalovirus (CMV) exposure on neonatal inflammatory profiles.
Main Methods:
- Whole-blood approach to quantify cytokine production.
- Stimulation of blood samples with Toll-like receptor (TLR) ligands (TLR1/2, TLR4, TLR7/8).
- Analysis of cytokine concentrations including IL-6, TNF-α, CXCL8, and IL-10.
Main Results:
- Full-term newborns showed significantly higher IL-6 and TNF-α concentrations after TLR7/8 stimulation compared to other groups.
- TLR7/8 stimulation potentiated pro-inflammatory responses (IL-6, TNF-α, CXCL8) in adults, while preterm newborns showed elevated TNF-α.
- Preterm newborns exhibited increased TLR1/2-induced IL-10, indicating altered inflammatory and immunosuppressive states.
Conclusions:
- Pilot results support further investigation into age-group differences in immune responses.
- TLR7/8 ligands show promise as potential vaccine adjuvant candidates for newborns.
- IL-10-targeted immunomodulation may offer therapeutic strategies for neonatal inflammatory diseases.
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) full-term 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 new-borns 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-IL-10, anti-IL-10 receptors, or anti-TLR1/2) might be a future therapeutic option for cases of overwhelming neonatal inflammatory diseases.
