A dysfunctional cytokine-mediated inflammatory response is implicated in the pathogenesis of neonatal disease, including periventricular leukomalacia and bronchopulmonary dysplasia (Jones et al. 1996; Yoon et al. 1997). The aim of this study was to characterise the chronological progress of the neonatal inflammatory response using an in vitro model based on lipopolysaccharide (LPS) stimulation of cord blood from term neonates.
Blood samples (n = 12) obtained with ethics approval were incubated in RPMI 1640 medium with and without 10 µg/ml LPS under a humidified 5 % CO2 atmosphere at 37 °C for 24 h. Their white cell count was determined in parallel. The concentrations of tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, interferon (IFN)-λ and IL-10 were determined by multiplex immunoassay at 0, 1, 3, 6 and 24 h of incubation. Potential secretory capacity (mean ± S.E.M.; expressed as pg/million white cells, WC) was defined as the difference between stimulated and control responses. Data were analysed by Kruskal-Wallis tests and post hoc Mann Whitney-U tests.
All cytokine secretory capacities increased significantly within 1 h (P < 0.001), which was less pronounced for IL-10 (P < 0.05). TNF-α secretory capacity peaked between 3-6 h (1, 581 ± 377 pg/million WC), and declined by 24 h. This pattern was also observed for IFN-λ, which peaked at 3 h, while the secretory capacities for IL-6, IL-8 (peak value 631 ± 75 pg/million WC) and IL-10 (peak value 311 ± 37 pg/million WC) increased throughout the incubation period. Overall IFN-λ secretory capacity was lowest (72 ± 10 pg/million WC) while that for IL-6 was greatest (61, 489 ± 7, 059 pg/million WC).
The neonatal inflammatory response is similar in chronological progress to that determined in adults. However, the comparatively low IFN-λ secretory profile suggests that a degree of immaturity in the neonatal response, likely associated with T-cell naive CD45RA+ phenotype. These results provide insight into the chronological progress of the neonatal inflammatory response, and may prove useful in improving our understanding of the aetiology of various neonatal complications and their treatment.
This work was supported by Cerebra.