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Allograft inflammatory factor-1 (AIF-1) was originally cloned from a rat heart allograft under chronic rejection. Data from many studies suggested an important role of AIF-1 in several inflammatory processes. The aim of this study was to examine the dynamic expression of AIF-1 and its association with the pathogenesis of hepatic schistosomiasis in BALB/c mice infected with S. japonicum. The expression of AIF-1 and tumour necrosis factor-alpha (TNF-α) was determined by enzyme-linked immunosorbent assay, western blot and immunohistochemistry. AIF-1 and TNF-α were overexpressed in hepatic tissues at the early stage of infection, and then diminished with the length of infection. On culturing splenocytes stimulated by soluble egg antigen for 72 h, the expression of AIF-1 in infected mice was suppressed, but TNF-α increased gradually. Our results showed that AIF-1 was overexpressed in the liver of BALB/c mice infected with S. japonicum, and the interaction between AIF-1 and TNF-α or other cytokines played an important role in the pathogenesis and progression of hepatic schistosomiasis.

To determine whether endothelin-1 (ET-1) in tracheal aspirates (TA) is a specific marker for acute lung injury in preterm infants with respiratory distress syndrome (RDS) who progress to bronchopulmonary dysplasia (BPD); and to investigate the relationship between TA ET-1 and the proinflammatory cytokines, interleukin-6 (IL-6) and IL-8, as early mediators of BPD.We measured TA ET-1, IL-6, and IL-8 levels in preterm infants whose lungs were mechanically ventilated for RDS, categorized into two groups, BPD or non-BPD, on the basis of oxygen requirement at 36 weeks' postconceptional age.A total of 106 TA samples were obtained from 34 infants with gestational ages ranging from 24 to 28 weeks on days 1, 3, 5, and 7 of life. There was a wide range of ET-1 concentration. TA ET-1 levels were significantly elevated on days 1, 3, and 7 in infants in whom BPD developed, in comparison with the non-BPD group (Mann-Whitney U test: p0.01). TA IL-8 levels were elevated on days 1, 3, 5, and 7 in the BPD group (p0.01); TA IL-6 levels were elevated (p0.05) only on day 5. There was a similarity in pattern of increase of TA ET-1 and TA IL-8 levels in the BPD group, with both being elevated in the first 24 hours of life and through the first week. There was no correlation between ET-1 and IL-8 values.Early significant increase in the TA ET-1 and IL-8 concentrations in preterm infants with acute lung injury correlates with subsequent progression to BPD.

The influx of inflammatory mediators and cells into the tracheobronchial effluent of preterm infants with respiratory distress syndrome (RDS) appears to be important in signaling the development of bronchopulmonary dysplasia (BPD). The mechanism that initiates this early inflammatory response is not well understood. The purpose of this study was to test the hypothesis whether increased interleukin-8 (IL-8), a potent chemoattractant for human neutrophils, appears in the airways of preterm infants with RDS in whom BPD develops before the influx of neutrophils. In addition, airway secretions were analyzed for the cytokine interleukin-6 (IL-6) to test the hypothesis whether this pro-inflammatory cytokine is an early marker of inflammation in preterm infants with RDS who progress to BPD. Sixty-five infants less than 32 weeks gestation with RDS were enrolled on the first day of life and 56 infants completed the study, with 31 recovering from RDS (Non-BPD) and 25 infants progressing to BPD. Infants were excluded from enrollment in the presence of maternal chorioamnionitis, infection at birth, or infection within the first week of life. There were no significant differences in birthweight, gestational age, or prolonged rupture of membranes between the two groups. Serial tracheal aspirates (TA) were collected on days 1, 3, 5, and 7 while the infants remained intubated. Significant elevations of TA neutrophil counts were detected in the BPD group on days 5 and 7. Cell-free TA revealed marked elevations of IL-8 in the BPD group compared to the Non-BPD group [median (25th percentile, 75th percentile), ng/ml epithelial lining fluid (ELF)] on day 1 [BPD 485 (195, 840); Non-BPD 63.1 (28.3, 197), P < 0.05] and day 3 [BPD 740 (319, 1310); Non-BPD 111 (54.3, 337); P < 0.05], while on days 5 and 7, the differences were not statistically significant. Interleukin-6 (IL-6) was measured as a marker of acute inflammation and was not different in the two groups on day 1, but was significantly elevated on day 3 [median (25th percentile, 75th percentile), ng/ml ELF; BPD 297 (62.1, 702); Non-BPD 72 (32.8, 266), P < 0.05] and on day 5 [BPD 270 (136, 672); Non-BPD 86.4 (57.8, 138), P < 0.05]. These studies demonstrate that elevation of IL-8 and IL-6 levels precedes the marked neutrophil influx seen in the TA of preterm infants in whom BPD develop. The presence of IL-8 and IL-6 in TA from these infants suggests that these cytokines either initiate the acute inflammatory cascade in the lungs, or they are early markers of the inflammatory process that places preterm infants at high risk for BPD.

The influx of inflammatory mediators and cells into the tracheobronchial effluent of preterm infants with respiratory distress syndrome (RDS) appears to be important in signaling the development of bronchopulmonary dysplasia (BPD). The mechanism that initiates this early inflammatory response is not well understood. The purpose of this study was to test the hypothesis whether increased interleukin-8 (IL-8), a potent chemoattractant for human neutrophils, appears in the airways of preterm infants with RDS in whom BPD develops before the influx of neutrophils. In addition, airway secretions were analyzed for the cytokine interleukin-6 (IL-6) to test the hypothesis whether this pro-inflammatory cytokine is an early marker of inflammation in preterm infants with RDS who progress to BPD. Sixty-five infants less than 32 weeks gestation with RDS were enrolled on the first day of life and 56 infants completed the study, with 31 recovering from RDS (Non-BPD) and 25 infants progressing to BPD. Infants were excluded from enrollment in the presence of maternal chorioamnionitis, infection at birth, or infection within the first week of life. There were no significant differences in birthweight, gestational age, or prolonged rupture of membranes between the two groups. Serial tracheal aspirates (TA) were collected on days 1, 3, 5, and 7 while the infants remained intubated. Significant elevations of TA neutrophil counts were detected in the BPD group on days 5 and 7. Cell-free TA revealed marked elevations of IL-8 in the BPD group compared to the Non-BPD group [median (25th percentile, 75th percentile), ng/ml epithelial lining fluid (ELF)] on day 1 [BPD 485 (195, 840); Non-BPD 63.1 (28.3, 197), P0.05] and day 3 [BPD 740 (319, 1310); Non-BPD 111 (54.3, 337); P0.05], while on days 5 and 7, the differences were not statistically significant. Interleukin-6 (IL-6) was measured as a marker of acute inflammation and was not different in the two groups on day 1, but was significantly elevated on day 3 [median (25th percentile, 75th percentile), ng/ml ELF; BPD 297 (62.1, 702); Non-BPD 72 (32.8, 266), P0.05] and on day 5 [BPD 270 (136, 672); Non-BPD 86.4 (57.8, 138), P0.05]. These studies demonstrate that elevation of IL-8 and IL-6 levels precedes the marked neutrophil influx seen in the TA of preterm infants in whom BPD develop. The presence of IL-8 and IL-6 in TA from these infants suggests that these cytokines either initiate the acute inflammatory cascade in the lungs, or they are early markers of the inflammatory process that places preterm infants at high risk for BPD.

Endothelin-1 (ET-1) is a potent vasoactive peptide that can induce a bronchopulmonary response via the generation of secondary mediators such as cyclooxygenase products and contribute to increased pulmonary vascular tone, both of which play significant roles in the mechanism of acute lung injury. The objectives of this study were to determine if ET-1 is a marker for pulmonary injury in infants with respiratory distress syndrome (RDS), and to demonstrate a possible relationship between ET-1 and proinflammatory cytokines IL-8 and IL-6 as early mediators of BPD. Preterm infants (34) ≤28weeks with RDS were included, 17 of whom progressed to BPD (oxygen requirement at 36 weeks postconceptional age). Clinical characteristics of the 2 groups were similar for gestational age (26.7 ± 0.3 vs 26.2 ± 0.3), birth weight (890 ± 45 vs 845 ± 40), maternal steroid therapy, cesarian delivery, surfactant replacement therapy, and oxygenation index on day 1. Tracheal aspirates (TA) were collected from intubated infants on days 1, 3, 5, and 7. ET-1, IL-8 and IL-6 levels were measured by ELISA and normalized for dilution by quantitative analysis of TA urea.Table

ET-1 is a potent vasoactive peptide, whose presence in the lungs may increase the production of oxygen radicals by alveolar macrophages, thus implicating ET-1 for a role in the pathogenesis of BPD. We hypothesized that TA ET-1 would be an early marker for pulmonary injury in infants with respiratory distress syndrome (RDS) and subsequent BPD (O2 requirement at 36 weeks post-conceptual age). We studied 19 preterm infants who had self-limiting RDS (n=10) and RDS that progressed to BPD (n=9). Demographic data (mean ± S.D.): Table TAs were collected from intubated infants at days 1, 3, & 5; cell-free supernatants were stored at -70° awaiting batch analysis. ET-1 levels were measured by ELISA(Peninsula Lab, Belmont, CA) and then corrected for dilution by quantitative analysis of TA urea. TA ET-1 levels (mean ±SE; ng/ml) are as follows:Table While there is no significant difference between the two groups on each day of analysis, there is a significant difference in the ET-1 levels in the TA of preterm infants who develop BPD. We speculate that the sustained elevation of ET-1 levels seen in those with acute lung injuries may reflect a role for ET-1 in the pathogenesis of BPD.

Tracheal aspirate(TA) samples obtained from ventilated preterm infants have been shown to contain detectable levels of the inflammatory markers IL-8 and IL-6 as well as PMNs, which have been implicated in the acute inflammatory response associated with the pathogenesis of BPD. We hypothesized that the presence of IL-8 and IL-6 in the TA in the early phase of lung injury in ventilated premature infants would predict the subsequent progression to BPD. Serial TAs were collected from ventilated premature neonates