This study shows that aggressive intake of AA and IL can be tolerated immediately after birth by VLBW infants. Also, ETPN significantly increased positive nitrogen balance and caloric intake, without increasing the risk of metabolic acidosis, hypercholesterolemia, or hypertriglyceridemia.

BackgroundGenetic variation in the innate immune system of the host may play a role in determining the risk of developing infection, as well as outcome from infection.MethodsInfectious complications were retrospectively determined in 293 (233 African-American (AA), 57 Caucasian and 3 Hispanic) mechanically ventilated very low birth weight (VLBW) infants (<1500 grams at birth) who were genotyped for the IL-6 -174 G/C, IL-10 -1082 G/A and CD14 -260 C/T single nucleotide polymorphisms (SNPs).ResultsThe IL-6 -174C allele was associated with an increased incidence of late blood stream infection (BSI) in AA but not Caucasian infants. In AA infants with the C allele the incidence of late BSI was 20/29 (69%) compared to 94/204 (46%) in homozygous GG infants (RR 2.6, 95% CI: 1.1–6.0, p = 0.021). The IL-10 -1082A allele was associated with an increased incidence of late BSI. One or more episodes of late BSI developed in 14 (35%) of 40 infants with the GG genotype, 71 (49%) of 145 infants with the GA genotype and 63 (58%) of 108 infants with the AA genotype (p = 0.036). Infants with the A allele (AA or GA genotypes) had an incidence of late BSI that was 134/253 (53%) compared to 14/40 (35%) in homozygous GG infants (RR 2.1, 95% CI: 1.04–4.19, p = 0.035). The CD14 -260 C/T SNP did not alter the overall risk for BSI in ventilated VLBW infants. Multiple BSI episodes were more common in the TT genotype group (CC: 17%, CT: 11%, TT: 30%, p = 0.022). This effect was due to the strong effect of the TT genotype on the incidence of multiple BSI in AA infants (CC: 15%, CT: 11%, TT: 39%, p = 0.003).ConclusionThe IL-6 -174 G/C, IL-10 -1082 G/A and CD14 -260 C/T SNPs may alter risk for BSI in ventilated VLBW infants.

Inflammation is one of the primary processes underlying respiratory distress syndrome (RDS) and its evolution into bronchopulmonary dysplasia (BPD). Recruitment and subsequent activation of macrophages in the lung are mediated by CC chemokines. The role of CC chemokines has not been extensively studied in the course of RDS. Serial tracheal aspirates (TA) were obtained from 56 mechanically ventilated infants with birth weights less than 1,500 g during intervals in the first 21 days of life. Tracheal aspirate concentrations of monocyte chemoattractant proteins-1,2,3 (MCP-1,2,3) and macrophage inflammatory proteins-1alpha and -1beta (MIP-1alpha, MIP-1beta) were determined by enzyme-linked immunosorbent assay (ELISA). Tracheal aspirate concentrations of MCP-1, MCP-2, MCP-3, and MIP-1beta increased during the first week of life in infants with RDS, whereas MIP-1alpha concentrations did not increase appreciably. Increased TA cytokine concentrations were associated with the development of BPD. Maximal TA concentrations of MCP-1, MCP-2, MCP-3, MIP-1alpha, and MIP-1beta were significantly higher in infants who were oxygen-dependent at 28 postnatal days compared to infant who were not. Similarly, maximal TA MCP-1, MCP-2, and MCP-3 but not MIP-1alpha and MIP-1beta concentrations were significantly higher in infants who were oxygen-dependent at 36 weeks of postconceptional age (PCA) than those who were not oxygen-dependent at 36 weeks PCA. Histologic chorioamnionitis and isolation of Ureaplasma urealyticum from the airways were associated with higher maximal TA concentrations of MIP-1alpha and MIP-1beta. Pulmonary hemorrhage was associated with increased maximal concentrations of MCP-1, MCP-2, and MCP-3. These data suggest a role for CC chemokines in the development of BPD in the newborn infant.

SUMMARY: Glomerulopathic monoclonal light chains (G-LC) interact with mesangial cells (MC), resulting in alterations ofmesangial homeostasis. Early signaling events control mitogenic activities and cytokine production, which in turn participate in the subsequent pathologic events. Mesangial homeostasis is affected in two very different ways, depending on whether the G-LC is from a patient with light chain deposition disease (LCDD) or light chain-related amyloidosis (AL-Am). In contrast, tubulopathic (T)-LC chains from patients with myeloma cast nephropathy do not significantly interact with MC and result in no alterations in mesangial homeostasis. Therefore, understanding early events in the monoclonal LC-MC interactions is fundamental. MC in culture were exposed to LC obtained and purified from the urine of patients with plasma cell dyscrasias and biopsy-proven renal disease, including LCDD, AL-Am, and myeloma cast nephropathy. Incubation of MC with G-LC, but not T-LC, resulted in cytoskeletal and cell shape changes, activation of platelet-derived growth factor-␤ (PDGF-␤) and its corresponding receptor, cytoplasmic to nuclear migration of c-fos and NF-␤ signals, and production of monocyte chemoattractant protein-1 (MCP-1), as well as increased expression of Ki-67, a proliferation marker. Although NF-␤ activation was directly related to MCP-1 production, c-fos activation regulated proliferative signals and cytoskeletal changes in MC. Amyloidogenic LC were avidly internalized by the MC, whereas LCDD-LC effector targets were located at the MC surface. These cellular events are likely initiated as a result of interactions of the G-LC with yet-uncharacterized MC surface receptors. Dissecting the events taking place when G-LC interact with MC may define potential important targets for selective therapeutic manipulation to ameliorate or prevent the glomerular injury that ensues. (Lab Invest 2001, 81:689 -703).

Due to developmental immaturity of the central nervous system, effects of an adverse intrauterine environment and need for intensive care postnatally, preterm infants are at high risk of sustaining brain injury in the perinatal period. Infants who suffer brain injury in the perinatal period are at risk for long-term neurodevelopmental sequelae. Clinical and experimental data supports a significant role for inflammatory mediators in the pathophysiology of perinatal brain injury. Abnormalities in coagulation proteins in the sick preterm newborn may accentuate the risk for intraventricular hemorrhage. Polymorphisms in TNF alpha , IL-1 beta , IL-4, IL-6 and IL-10 as well as mutations in coagulation proteins have been investigated as potential candidate genes to modify risk and or severity of perinatal brain injury. Preliminary evidence suggests a role for cytokine genes as risk modifiers for IVH and PVL.