Inflammatory signatures and immunomodulation in neonates: a pilot study.

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.