Thomas E Kruger

Failure of erythromycin to eliminate airway colonization with ureaplasma urealyticum in very low birth weight infants

BackgroundAirway colonization of mechanically ventilated very low birth weight infants (birth weight < 1500 grams) by Ureaplasma urealyticum (Uu) is associated with an increased risk of bronchopulmonary dysplasia (BPD). While Uu is sensitive to erythromycin in vitro, the efficacy of intravenous (IV) erythromycin to eliminate Uu from the airways has not been studied.Methods17 very low birth weight infants with Uu positive tracheal aspirate (TA) cultures were randomized to either 5 (8 infants) or 10 days (9 infants) of IV erythromycin lactobionate (40 mg/kg/day in 3 divided doses). Tracheal aspirate cultures for Uu were performed on days 0, 5, 10 and 15.ResultsIntravenous erythromycin failed to eliminate airway colonization in a large proportion of infants regardless of whether they received 5 or 10 days of treatment. Ureaplasma urealyticum was isolated from 4/15 (27%) of TAs obtained at 5 days, 5/12 TAs (42%) obtained at 10 days and 6/11(55%) TAs obtained at 15 days (combined group data).ConclusionsErythromycin administered IV does not eliminate Uu from the airways in a large proportion of infants. Failure of erythromycin to eliminate Uu from the airways may contribute to the lack of efficacy of this drug in reducing the incidence of BPD in very low birth weight infants.

Tumor necrosis factor alpha -- 308 polymorphism associated with increased sepsis mortality in ventilated very low birth weight infants.

Background: Sepsis commonly complicates the clinical course of critically ill very low birth weight infants, with as many as 30% developing hospital-acquired bacteremia. The tumor necrosis factor &agr; (TNF-&agr;) −308 G/A single nucleotide polymorphism (SNP) is associated with adverse outcome in septic adult patients. Methods: One hundred seventy-three mechanically ventilated very low birth weight infants were genotyped for the TNF-&agr; −308 G/A SNP. Results: One hundred twenty (69%) infants were homozygous GG, 45 (26%) were heterozygous AG and 8 (5%) were homozygous AA; 2 of 120 (2%) infants developed early bacteremia in the GG group, and 1 of 53 (2%) developed early bacteremia in the AA/AG group (P = 0.919). One or more episodes of late bacteremia/fungemia developed in 59 of 120 (49%) infants with the GG genotype and 23 of 53 (43%) infants with the AG/AA genotype (P = 0.484). Endotracheal tube colonization rates were 65 of 120 (54%) for infants with the GG genotypes and 28 of 53 (53%) for infants with the AG/AA genotypes (P = 0.871). Nosocomial pneumonia developed in a similar number of infants in both genotype groups (9 of 120 infants vs. 3 of 53 infants; P = 0.461). Mortality from sepsis was 3 times greater in infants with the AA/AG genotypes than in those with the GG genotype (10%vs. 3%; P = 0.038). This difference in sepsis mortality was even greater when only bacteremic/fungemic infants are considered (4 of 59 infants vs. 6 of 23 infants; P = 0.026). Conclusions: These data suggest that the TNF-&agr; −308 A allele does not affect the development of sepsis in ventilated premature infants but may increase mortality once sepsis develops.

Immunomodulation of peripheral lymphocytes by hormones of the hypothalamus-pituitary-thyroid axis

The aim of this review is to provide a comprehensive examination of the current literature describing the immunoregulatory effects on the peripheral immune system by the hormones that comprise the hypothalamic-pituitary-thyroid (HPT) axis. This article discusses the effects of the HPT axis hormones on the peripheral lymphoid tissues and the immune responses mediated by the cells that comprise these lymphoid tissues. Neuroendocrine dysfunction in the HPT axis, either naturally or experimentally induced, and the resulting immune dysfunction are also discussed. Emphasis in this article is placed on the most recent study findings and those that provide a unique or novel way of evaluating HPT hormone effects on the immune system. Our knowledge of the immunoregulatory effects of the hormones that comprise the HPT axis has grown tremendously in the last 10 years. As can be seen in this review, the immunoregulatory effects of the HPT axis hormones are quite diverse and influence most, if not all, aspects of immune system physiology. The continued exploration of the bidirectional circuitry between the immune and neuroendocrine systems may allow for development of appropriate prophylactic procedures that prevent dysfunction in both systems.

Ethanol-Induced Suppression of in Vivo Host Defense Mechanisms to Bacterial Infection

Study findings have shown that chronic ethanol (ETOH) abuse causes individuals to have an increased incidence of infections related to opportunistic and pathogenic organisms (1–3). This is particularly true for bacterial pneumonias, which cause greater mortality in alcoholics as compared with nonalcoholics. Alcoholics also have an increased incidence of tumors of the head, neck, and gastrointestinal tract (4,5). Individuals with alcohol-induced liver cirrhosis have circulating lymphocytes that are cytotoxic to hepatocytes, suggesting that ETOH may induce an immune dysfunction that leads to autoimmunity (6-8). Although the exact role of ETOH in these diseases is not well understood, its effects on both specific and nonspecific aspects of immune function are thought to be involved. With ETOH consumption, many of the nonspecific aspects of immune function are altered. For example, consumption of ETOH by mice leads to depressed natural killer cell activity (9). Ethanol consumption also results in diminished granulocyte function such as decreased phagocytosis and altered migration to chemotactic factors by polymorphonuclear leukocytes (10,11). Ethanol directly alters monocyte and macrophage functions in human beings and experimental animals. For example, exposure of human macrophages to ETOH in vitro reduces the production and release of lysozyme, as well as the total number of macrophages containing lysozyme (12). Furthermore, study findings have shown that ETOH impairs phagocytosis in human monocytes and macrophages (13). Similar results have been obtained by investigators examining the effects of ETOH on rat peritoneal, alveolar, and splenic macrophages (14,15).

Interleukin-4 and 13 concentrations in infants at risk to develop Bronchopulmonary Dysplasia.

BackgroundAn exaggerated inflammatory response occurs in the first few days of life in infants who subsequently develop bronchopulmonary dysplasia (BPD). The increase of inflammatory cytokines in many disease processes is generally balanced by a rise in anti-inflammatory cytokines. Interleukin-4 (IL-4) and interleukin-13 (IL-13) have been shown to inhibit production of several inflammatory cytokines important in the development of BPD.MethodsWe sought to determine if a correlation exists between the presence or absence of IL-4 and IL-13 in tracheal aspirates (TA) during the first 3 weeks of life and the development of BPD in premature infants. Serial TAs were prospectively obtained from 36 very low birth weight infants and IL-4 and IL-13 concentrations were determined by ELISA.ResultsInfants who developed BPD (n = 19) were less mature (25.3 ± 0.02 wks vs. 27.8 ± 0.05 wks; p < 0.001), and had lower birth weights (739 ± 27 g vs.1052 ± 41 g; p < 0.001). IL-4 and IL-13 were detectable in only 27 of 132 and 9 of 132 samples assayed respectively. Furthermore, the levels detected for IL-4 and IL-13 were very low and did not correlate with the development of BPD.ConclusionsTA concentrations of IL-4 and IL-13 do not increase significantly during acute lung injury in premature infants.

Thrombin Induces Interleukin-8 (IL-8) and Monocyte Chemoattractant Protein-1 (MCP-1) in Alveolar Type II Cells

Thrombin Induces Interleukin-8 (IL-8) and Monocyte Chemoattractant Protein-1 (MCP-1) in Alveolar Type II Cells

Pulmonary Hemorrhage (PH) Is Associated with Increased Tracheal Concentrations of Pro-Inflammatory Cytokines and Increased Risk of Bronchopulmonary Dysplasia (BPD)

Pulmonary Hemorrhage (PH) Is Associated with Increased Tracheal Concentrations of Pro-Inflammatory Cytokines and Increased Risk of Bronchopulmonary Dysplasia (BPD)

Monocyte chemoattractant protein (MCP-1) is increased in tracheal aspirates of infants that develop bronchopulmonary dysplasia (BPD). 1606

Monocyte chemoattractrant protein-1 (MCP-1), a monocyte chemoattractrant and activating chemokine has been implicated in the pathogenesis of fibrotic lung diseases. We wanted to determine if tracheal aspirate concentrations of MCP-1 correlated with the development of BPD (defined as requirement for supplemental oxygen with compatible Xray changes at 28 days). Tracheal aspirates were obtained from 24 very low birth weight infants during the first 2 weeks of life. Concentrations of MCP-1 and secretory component of IgA concentrations were determined by ELISA. Concentrations of MCP-1 were normalized to secretory component, which does not change with inflammation or steroid use. Tracheal concentrations of MCP-1 increased from day 1 through day 5 in infants with RDS. However, infants with BPD had significantly greater concentrations of MCP-1 than infants that did not develop BPD at all days examined.These results demonstrate a correlation between increased MCP-1 concentrations and the development of BPD. Thus MCP-1 production and subsequent macrophage activation may contribute to the pathogenesis observed in BPD. Concentrations of MCP-1 are expressed as pg MCP-1/ug Secretory Component. Data represent Mean±SE (*p<0.05). Table

Interleukin-4 (IL-4) and Interleukin-13 (IL-13) inhibit IL-1β induction of Interleukin-8 (IL-8) and Epithelial neutrophil activating protein (ENA-78) in alveolar type II cells. 1958

Alveolar type II cells participate in inflammatory processes of the lung by elaborating chemotactic cytokines in response to IL-1β. Since IL-4, IL-13 and IL-10 have been shown to influence macrophage production of inflammatory cytokines, particularly IL-8, we assessed the ability of these cytokines to modify IL-1β induced chemokine release in type II cells. A549 cells were incubated with 100 ng/ml of IL-4,10 and 13 for 24 hours prior to the addition of 50 pg /ml IL-1β. Culture supernatants were examined for IL-8, MCP-1 and ENA-78 after 24 hours incubation. Interleukin-4 and IL-13 significantly inhibited IL-1β induced IL-8 and ENA-78 production. Interleukins 4, 10 and 13 (100 ng/ml) alone had no effect on IL-8 or ENA-78 production. Our results suggest that IL-4 and IL-13 may regulate chemokine production in alveolar type II cells. In contrast to its effects in macrophages, IL-10 has little effect on IL-8, MCP-1 or ENA-78 production in type II cells. Data represent Mean±SE of 7 experiments.(*p<0.05;#p=0.06) Table

Differential Regulation of Interleukin-8 (IL-8) and ENA-78 in Alveolar Type II Cells (A549) by Retinoic Acid. † 1287

Differential Regulation of Interleukin-8 (IL-8) and ENA-78 in Alveolar Type II Cells (A549) by Retinoic Acid. † 1287