Yasunori Koike

Cytokine profiles of seventeen cytokines, growth factors and chemokines in cord blood and its relation to perinatal clinical findings.

Few papers have investigated the cytokine profiles of multiple cytokines in cord blood. We obtained cord blood samples from 224 infants admitted to our neonatal intensive care unit. Cytokine profiles of 17 cytokines were investigated using cytometric bead array technology. We found a wide variety of cytokines of various levels which ranged from 0.59pg/ml (in Interleukin (IL)-4) to 222.0pg/ml (in macrophage inflammatory protein-1beta. Pro-inflammatory cytokines were highly correlated with each other and with granulocyte-colony stimulating factor and IL-8. On the contrary, IL-5, IL-13, and IL-17 did not show any significant correlation with other cytokines. Several maternal factors were strongly related to several cytokines in cord blood. IL-6, IL-8 and monocyte chemotactic protein-1 were closely related to certain neonatal diseases in preterm neonates. Some cytokines may be regulated independently of each other, while others appear to work as a network affecting physiological and pathological conditions in the fetus.

Prolonged maternal magnesium administration and bone metabolism in neonates

BACKGROUND Magnesium sulfate (MgSO(4)) has been used as a tocolytic agent in cases of refractory preterm labor. Prolonged maternal administration of MgSO(4) may induce bone demineralization in the neonate. However, the effects of MgSO(4) on serum biochemistry related to bone metabolism in neonates remain unclear. AIM To assess the effects of prolonged maternal administration of MgSO(4) on fetuses and neonates. STUDY DESIGN This retrospective case-control study examined 167 neonates. Cases comprised 58 neonates whose mothers had received intravenous MgSO(4) administration for >5 days. Neonatal serum levels of magnesium (Mg), calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) were reviewed. We also investigated whether subject neonates showed appearance of osteopenia at the metaphyseal lines on radiography at birth. RESULTS Mean serum Mg and P levels were significantly higher, and Ca levels were significantly lower, in cases than in controls at birth. Mean serum ALP level was 1188.5IU/l in cases, significantly higher than that in controls at birth. Bone abnormalities were noted on radiography in 2 subjects. By 3 weeks old, serum ALP levels did not differ significantly between cases and controls. Logistic regression analysis revealed maternal administration of MgSO(4) and multiple pregnancies were significantly related to serum ALP level in neonates at birth. CONCLUSION Prolonged maternal administration of MgSO(4) significantly affects neonatal serum biochemistry related to bone metabolism. Potential long-term adverse effects on neonates and how Mg affects fetal bone metabolism in utero need to be investigated in future studies.

Selective excretion of anti-inflammatory cytokine interleukin-10 in a superantigen-inducing neonatal infectious disease.

Neonatal toxic shock syndrome (TSS)-like exanthematous disease (NTED) is an emerging neonatal infectious disease caused by TSS toxin-1 (TSST-1). Although NTED and TSS are caused by the same superantigenic exotoxin, NTED is less severe than TSS. The mechanism of this reduced severity in NTED has not been elucidated. Thirteen patients with NTED were enrolled in the study. We investigated serum cytokine profile using a cytometric bead array system with a cytokine panel. Expression of Vbeta2 and CD45RO in CD4(+) T cells was investigated in mononuclear cells by using flowcytometry. Ten patients with other bacterial infections and eight patients without any infections were also enrolled as control groups. The mean serum level of IL-10 was 1209.9 pg/mL in patients with NTED at the time of admission into the study. The other inhibitory cytokine, IL-4, exhibited a minimum level. The high level of IL-10 rapidly decreased within 3-9 days of the onset of NTED. The cytokine profile of NTED, with its high IL-10 level, was clearly different from that of the other bacterial infections. The increased level of IL-10 seems to be related to the reduced severity of NTED. Th2 shift is not thought to be the cause of this IL-10 excretion.

Gut hormone profiles in preterm and term infants during the first 2 months of life.

Abstract Aim: To investigate changes of gut hormones in term and preterm infants in the first 2 months after birth, as the role and relationships of gut hormones in premature infants has not been well elucidated. Methods: In 29 preterm and five term infants, fasting serum concentrations of leptin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide, insulin, amylin, and ghrelin were measured using a bead array system. Results: Serum leptin concentration soon after birth showed a positive correlation with gestational week in all infants (r=0.623, p<0.01). Serum leptin level rapidly decreased in all infants. In preterm infants, serum GLP-1 levels at birth showed negative correlations with gestational week (r=–0.447, p=0.02). Serum GIP, GLP-1, and PYY levels increased after birth and were persistently high until 10 weeks of life. Conclusion: Serum concentrations of different gut hormones changed postnatally in their specific ways in preterm infants.

Hemophagocytic lymphohistiocytosis in a newborn infant born to a mother with Sjögren syndrome antibodies.

We encountered a neonatal patient with hemophagocytic lymphohistiocytosis (HLH) whose mother was positive for anti-Ro/SSA and anti-La/SSB antibodies. Complete atrioventricular block was found in a male patient at 29 weeks of gestation. The patient was born at 40 weeks of gestation. He showed severe circulatory disturbance at 22 h after the birth, and he also had elevated serum levels of aspartate aminotransferase (1027 IU l−1), alanine aminotransferase (121 IU l−1), lactic dehydrogenase (3490 IU l−1), ferritin (9769.7 ng ml−1) and soluble interleukin-2 (IL-2) receptor (3230 U ml−1). We could not find any known HLH genetic abnormality in the patient, but he fulfilled seven of the eight criteria for HLH. Serum levels of IL-6 and IL-8 had been already elevated in his cord blood, and serum levels of granulocyte-macrophage colony-stimulating factor and IL-8 were significantly increased on the second day of life. His symptoms regressed with the administration of hydrocortisone. We presumed that transplacental transfer of maternal antibodies could be related to the occurrence of HLH.

Congenital hemophagocytic lymphohistiocytosis in a preterm infant: cytokine profile and a review of the disease.

A preterm infant with very low birth weight was born with fetal onset familial hemophagocytic lymphohistiocytosis. Known gene abnormalities responsible for the disease were not identified in the patient. The infant died at 13 months of age owing to complications from cord blood stem cell transplantation. We found selectively elevated expression of interleukin-6 and chemokines in the cord blood of the patient. We also reviewed 7 other preterm cases of congenital hemophagocytic lymphohistiocytosis to highlight the significance of this condition, as it can cause ascites and hepatosplenomegaly in utero and be mistaken for congenital infection in the fetus.

Selectively High Level of Serum Interleukin 5 in a Newborn Infant With Cow's Milk Allergy

Cows milk allergy (CMA) in the neonatal period is thought to include several clinical conditions, yet the pathophysiology remains unclear. We report here the case of a term newborn infant who showed hematochezia 36 hours after the first feeding with cows milk formula. His serum immunoglobulin E levels were not elevated, although eosinophils were detected in the stool. Elimination of cows milk formula resolved the symptoms, and from the clinical course and laboratory data the infant was diagnosed with CMA. The serum interleukin 5 (IL-5) (125 pg/mL) level in this patient was selectively elevated. However, serum levels of other T-helper 2 (Th2) cytokines (including IL-4 and IL-13), Th1 cytokines (including interferon γ), and proinflammatory cytokines (including tumor necrosis factor α) were not elevated. These findings suggest that, for this patient, IL-5 and eosinophils might have played a role in the development of neonatal CMA. Although this finding is reported from only 1 case, it highlights the need for serum IL-5 to be determined in more neonatal patients with CMA to further clarify the pathophysiology of this condition in the neonatal period.

Association of development of chronic lung disease of newborns with neonatal colonization of Ureaplasma and cord blood interleukin‐8 level

Background:  The aim of the present study was to investigate the association of chronic lung disease (CLD), neonatal Ureaplasma colonization, and interleukin‐8 (IL‐8) level of cord blood in preterm infants.

Selectively High Levels of Serum Interleukin 17 in a Newborn Infant With Progressive Severe Cholestasis

We present here the unusual case of a male newborn infant who showed progressive severe cholestasis. The infants gestational age was 37 weeks, and his birth weight was 2134 g. His serum level of direct bilirubin gradually increased from the 6th day of life and reached 257.5 μmol/L on the 22nd day of life. We could not find any cause for his cholestasis, but his serum level of ferritin was extremely elevated at 9211.0 ng/mL. Because we felt that his clinical condition might be related to hypercytokinemia caused by an immunologic reaction, steroid pulse therapy and cyclosporine were administered. His condition improved, and his direct bilirubin and ferritin levels declined. From the investigation of his cytokine profile, we found a preferentially elevated level of serum interleukin 17 (IL-17) (96.1 pg/mL) and high level of chemokines IL-8 and macrophage inflammatory protein 1β. The IL-17 level gradually decreased to 7.5 pg/mL by the 124th day of life. The infant was successfully discharged from the childrens hospital but later developed epilepsy at 11 months and asthma at 1 year, 2 months of age. Although we have not yet reached a definitive diagnosis, this case may be the first to show a relationship between cholestasis and an elevated serum IL-17 level in the neonatal period.

Hypothyroxinemia and effectiveness of thyroxin supplementation in very low birth weight infants with abdominal distension and poor weight gain

BACKGROUND Very low birth weight (VLBW) infants sometimes develop abdominal distension and poor weight gain. The influence of thyroid function on these symptoms in VLBW infants has not been reported. METHODS In a retrospective study, 18 VLBW infants whose abdominal distension and poor weight gain did not improve with standard treatment were enrolled as subjects. Serum levels of free thyroxin (fT(4)) and thyroid stimulating hormone (TSH) were measured. Subjects with serum fT(4) levels less than 1.3 ng/dl received thyroxin supplementation. Another 18 VLBW infants were recruited as age- and weight-matched controls. We compared degree of intestinal dilation on X-ray, weight gain, and quantity of milk tolerated before and after starting thyroxin supplementation in the subjects and the controls. RESULTS All subjects had serum fT(4) levels less than 1.3 ng/dl (mean, 0.72 ng/dl). TSH values varied widely and were less than 8 microU/ml in 12 subjects. Therefore, all subjects received thyroxin supplementation; after starting this, mean serum fT(4) level increased significantly to 1.31 ng/dl. In parallel with fT(4) increase, intestinal dilation improved in 16 of 18 subjects (mean grade of dilation decreased from 2.8 to 1.6). Weight gain and quantity of tolerated milk were significantly increased with thyroxin supplementation in all and 17 of the 18 subjects, respectively. CONCLUSIONS Thyroxin supplementation was effective in improving abdominal symptoms in VLBW infants whose serum fT(4) level was less than 1.3 ng/dl.