Tumor necrosis factor-alpha, IL-1 beta, and IL-6 are thought to be involved in the pathogenesis of sepsis with gram-negative bacteria. We studied these cytokines during neonatal sepsis with mainly gram-positive bacteria. Ten newborns with clinical sepsis and 22 healthy controls were enrolled in the study. TNF alpha plasma levels proved to be increased in the newborns with sepsis up to 560 +/- 234 pg/mL (ng/L) versus 36 +/- 4 pg/mL (ng/L) in the control group (p < 0.005), whereas IL-6 plasma levels in newborns with sepsis were 79.700 +/- 37.500 pg/mL (ng/L) versus 55 +/- 28 pg/mL (ng/L) in the control group (p < 0.01). The IL-1 beta plasma levels were only slightly elevated in the group newborns with sepsis [up to 18 +/- 5 pg/mL (ng/L) versus 7 +/- 1 pg/mL (ng/L) in the control group (p < 0.01)]. After the start of therapy with antibiotics, both TNF alpha and IL-6 plasma levels decreased concomitantly with the improvement of the clinical situation within 2 d. These data confirm the abundant presence of TNF alpha and IL-6 during neonatal sepsis, whereas IL-1 beta appeared to be present in small amounts only. Nevertheless, the IL-1 beta but not the TNF alpha plasma level appeared to correlate inversely with the decrease in diastolic tension as standardized according to birth weight (R = 0.66, p = 0.04). TNF alpha, IL-1 beta, and IL-6 were not correlated with any febrile response in the group with sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

The concentration of soluble transferrin receptors in serum has proven to be a reliable predictor of iron status in adults. Its high sensitivity for iron deficiency combined with a small sample size (10 microliters) makes it an interesting parameter for the assessment of iron stores in newborn infants. In the present study we investigated the usefulness of the concentration of soluble transferrin receptors in serum in the assessment of iron metabolism in the newborn. Infants born after an uncomplicated labour were compared to infants in the intensive care unit. The concentration of soluble transferrin receptors in serum was found to be elevated compared to normal adults and independently of iron metabolism. The concentration of soluble transferrin receptors did not correlate with serum iron and ferritin concentrations. In contrast to what was found in other studies, no relationship could be demonstrated between soluble transferrin receptors and birth weight or gestational age. The results of this study have shown that care has to be taken in the interpretation of the concentration of soluble transferrin receptors in serum in newborn infants. It seems to be a parameter which is independent of iron metabolism at least during the first days of life.

The expression of transferrin receptors on the cell membrane of erythroblasts was analysed with flow cytometry in patients with different forms of anaemia. At the same time the concentration of soluble transferrin receptors (sTfRs) was analysed in serum. It was shown that only in iron deficiency a high concentration of sTfRs in serum could be explained with an increased expression of transferrin receptors on the erythroblastic membrane. In anaemia of chronic disease and myelodysplasia a discrepancy between a low expression on the cell membrane and normal or elevated serum values was seen. From this study we conclude that the concentration of sTfRs in serum does not only depend on the expression of transferrin receptors on the erythroblasts but also on the erythroid activity.

Summary:In this study the analytical performances of two recently introduced assays for soluble transferrin receptors in serum were tested. The Ramco transferrin assay was compared with the Eurogenetics assay. In a small clinical study serum samples from patients with anaemia of chronic disease, iron deficiency and myelodysplastic syndrome were analysed, as well as sera from healthy volunteers. The analytical performances of the Ramco assay were found to be acceptable. In the Eurogenetics test however, inter-assay imprecision and the end of run drift were unacceptably high. We were able to confirm that in patients with uncomplicated iron deficiency the concentration of soluble transferrin receptors is higher than in healthy volunteers. In cases of anaemia of chronic and inflammatory disease, the levels of soluble transferrin receptors in serum are slightly, but not significantly, higher than in normal subjects. Measurement of soluble transferrin receptors in serum provides a good differentiation between anaemia of chronic disease and iron deficiency.

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