ORIGINAL ARTICLE

Proinflammatory and anti-inflammatory cytokine responses in preterm infants with systemic infections

P C Ng¹, K Li¹, R P O Wong¹, K Chui¹, E Wong², G Li¹ and T F Fok¹

¹ Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
² Centre of Clinical Trials and Epidemiological Research, Prince of Wales Hospital

Correspondence to:
Correspondence to:
Professor Ng, Department of Paediatrics, Level 6, Clinical Sciences Building, Prince of Wales Hospital, Shatin, NT, Hong Kong;
pakcheungng{at}cuhk.edu.hk

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) , and tumour necrosis factor (TNF) , 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, IFN, TNF) and anti-inflammatory (IL4, IL10) cytokines were significantly increased in infected infants compared with non-infected infants. Significant correlations were observed between IL6 and TNF or IL10 as well as IL10 and IFN in infected infants. In the subgroup analysis, plasma IL6, IL10, and TNF concentrations, and IL10/TNF and IL6/IL10 ratios were significantly elevated in patients with disseminated intravascular coagulation compared with infected infants without. The IL10/TNF 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 TNF concentrations, and IL10/TNF and IL6/IL10 ratios signify severe infection, but transiently elevated plasma IL10 concentration or IL10/TNF ratio does not necessarily indicate a poor prognosis.

Keywords: cytokines; infection; preterm

Abbreviations: IFN, interferon; IL, interleukin; TNF, tumour necrosis factor; VLBW, very low birthweight; NEC, necrotising enterocolitis; CRP, C reactive protein; DIC, disseminated intravascular coagulation

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