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

Objective. To assess the effectiveness of a “stress dose” of hydrocortisone for rescue treatment of refractory hypotension and adrenocortical insufficiency of prematurity in very low birth weight (VLBW) infants. We hypothesized that significantly more VLBW infants who were receiving dopamine ≥10 μg/kg per min could wean off vasopressor support 72 hours after treatment with hydrocortisone.Methods. A double-blind, randomized, controlled study was conducted in a university neonatal center. Forty-eight VLBW infants who had refractory hypotension and required dopamine ≥10 μg/kg per min were randomly assigned to receive a stress dose of hydrocortisone (1 mg/kg every 8 hours for 5 days; n = 24) or an equivalent volume of the placebo solution (isotonic saline; n = 24).Results. The baseline clinical characteristics were similar between the groups. Serum cortisol concentrations were very low immediately before randomization in both groups of infants. Significantly more VLBW infants who were treated with hydrocortisone weaned off vasopressor support 72 hours after starting treatment. The use of volume expander, cumulative dose of dopamine, and dobutamine were significantly less in hydrocortisone-treated infants compared with control infants. In addition, the median duration of vasopressor treatment was halved in hydrocortisone-treated patients. Two versus 11 infants in the hydrocortisone and control groups required a second vasopressor for treatment of refractory hypotension. The trend (linear and quadratic) of the mean arterial blood pressure was also significantly and consistently higher in hydrocortisone-treated infants.Conclusions. A stress dose of hydrocortisone was effective in treating refractory hypotension in VLBW infants. Although routine and prophylactic use of systemic corticosteroids could not be recommended because of their potential adverse effects, this relatively low dose of hydrocortisone would probably be preferable to high-dose dexamethasone for treatment of refractory hypotension in emergency and life-threatening situations.

To review the current evidence on the use of infection markers for diagnostic evaluation of sepsis in neonates. Recent research in immunology has led to the discovery of cell surface antigens, chemokines, cytokines and acute phase proteins that can potentially be used to 'rule in' or 'rule out' sepsis. The diagnostic utilities of key inflammatory mediators, including CD11b, CD64, interleukin-6 and interleukin-8, are promising and likely to become increasingly used as markers of infection for both diagnostic and prognostic purposes. Serial measurements and use of combinations of markers have been reported to improve sensitivity and negative predictive value of these tests. Current markers are not infallible, however, and do not permit neonatologists to withhold antibiotics in sick infants with suspected infection. Thus, many have emerged as useful indicators for early discontinuation of unnecessary antimicrobial therapy. Some infection markers are also useful for identifying infants with severe infection and adverse prognosis. Advances in flow cytometry have allowed simultaneous measurement of key markers using only minimal blood volume. Judicious selection of a panel of markers with complementary properties could greatly increase the ability of neonatologists to diagnose infection and discern valuable prognostic information.

Very low birth weight (VLBW) infants with suspected late-onset infection requiring sepsis screening were enrolled in a prospective study to evaluate the diagnostic utilities of a comprehensive panel of key chemokines and cytokines, both individually and in combination, to identify diagnostic markers for early recognition of bacterial sepsis and necrotizing enterocolitis (NEC). Plasma chemokines interleukin (IL)-8, interferon-γ–inducible protein 10 (IP-10), monokine induced by interferon-γ (MIG), monocyte chemoattractant protein 1 (MCP-1), growth-related oncogene-α (GRO-α), and regulated upon activation of normal T cell expressed and secreted (RANTES) and cytokines IL-1β, IL-6, IL-10, IL-12p70, and tumor necrosis factor α (TNF-α) were measured at the onset of sepsis (0 h) and 24 h later. Of 155 suspected infection episodes, 44 were classified as infected. Concentrations of all studied inflammatory mediators (except IL-1β and RANTES) were significantly higher in the infected than in the noninfected group at 0 h, but the levels decreased precipitously by 24 h. IP-10 with a plasma cutoff concentration ≥1250 pg/mL could identify all septicemic and NEC cases and had the highest overall sensitivity (93%) and specificity (89%) at 0 h. We conclude that preterm infants have the ability to induce a robust chemokine and cytokine response during sepsis, and IP-10 is a sensitive early marker of infection.