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Proinflammatory and anti-inflammatory cytokine responses in preterm infants with systemic infections
P C Ng1, K Li, R P O Wong
1Department of Paediatrics, Level 6, Clinical Sciences Building, Prince of Wales Hospital, Shatin, NT, Hong Kong. pakcheungng@cuhk.edu.hk
Insights
In preterm infants, both pro-inflammatory and anti-inflammatory cytokines increase during systemic infection. Elevated levels of IL-6, IL-10, and TNF-alpha indicate severe infection, but do not always predict poor outcomes.
Area of Science:
- Neonatal immunology
- Critical care medicine
- Pediatric infectious diseases
Background:
- Systemic infections pose significant risks to preterm infants.
- Understanding cytokine responses is crucial for managing neonatal sepsis.
Purpose of the Study:
- To investigate the patterns of pro-inflammatory and anti-inflammatory cytokine responses in preterm infants with systemic infection.
- To correlate cytokine levels with infection severity and clinical outcomes.
Main Methods:
- Prospective study of very low birthweight infants with suspected infection.
- Measurement of key cytokines (IL-2, IL-4, IL-5, IL-6, IL-10, IFN-gamma, TNF-alpha) at multiple time points.
- Analysis using flow cytometry and immunoassay.
Main Results:
- Both pro-inflammatory and anti-inflammatory cytokines were elevated in infected infants.
- Significant correlations were found between IL-6, IL-10, and TNF-alpha.
- Elevated IL-6, IL-10, and TNF-alpha, and specific cytokine ratios, were associated with disseminated intravascular coagulation and mortality.
Conclusions:
- A counter-regulatory cytokine mechanism is likely active in preterm infants.
- High concentrations of IL-6, IL-10, and TNF-alpha indicate severe infection.
- Transient elevations in IL-10 or IL-10/TNF-alpha ratio do not necessarily predict a poor prognosis.
Objective:
A prospective study to investigate the pattern of proinflammatory and anti-inflammatory cytokine responses in preterm infants with systemic infection.
Methods:
Very low birthweight infants in whom infection was suspected when they were > 72 hours of age were eligible. A full sepsis screen was performed in each episode. Key cytokines of both proinflammatory and anti-inflammatory pathways, including interleukin (IL) 2, IL4, IL5, IL6, IL10, interferon (IFN) gamma, and tumour necrosis factor (TNF) alpha, were measured at 0 (at the time of sepsis evaluation), 24, and 48 hours by flow cytometric analysis or immunoassay.
Results:
Thirty seven of the 127 episodes of suspected clinical sepsis were proven infection or necrotising enterocolitis. Both proinflammatory (IL2, IL6, IFNgamma, TNFalpha) and anti-inflammatory (IL4, IL10) cytokines were significantly increased in infected infants compared with non-infected infants. Significant correlations were observed between IL6 and TNFalpha or IL10 as well as IL10 and IFNgamma in infected infants. In the subgroup analysis, plasma IL6, IL10, and TNFalpha concentrations, and IL10/TNFalpha and IL6/IL10 ratios were significantly elevated in patients with disseminated intravascular coagulation compared with infected infants without. The IL10/TNFalpha ratios had decreased significantly 48 hours after the onset, whereas the IL6/IL10 ratio showed only a non-significant decreasing trend. Further, the IL6/IL10 ratio in the deceased infant was disproportionally increased at presentation and continued to increase despite treatment.
Conclusion:
The results indicate that the counter-regulatory mechanism between the proinflammatory and anti-inflammatory cytokine pathways is probably operational in preterm infants of early gestation. High plasma IL6, IL10, and TNFalpha concentrations, and IL10/TNFalpha and IL6/IL10 ratios signify severe infection, but transiently elevated plasma IL10 concentration or IL10/TNFalpha ratio does not necessarily indicate a poor prognosis.