Exogenous Bovine Surfactant Suppresses Tumor Necrosis Factor‐α Release by Murine Macrophages Stimulated by Genital Mycoplasmas

Talati, Ajay J.; Crouse, Dennis T.; English, B. Keith; Newman, Cynthia; Livingston, Lisa; Meals, Elizabeth

doi:10.1086/515695

Cited by 12 publications

(10 citation statements)

References 14 publications

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“…Likewise, many infants may harbor respiratory syncytial virus but not develop significant lower respiratory tract infection. Differences in virulence by serovar subtype, maternal-fetal-neonatal immune system response, and intrinsic pulmonary defense factors, such as surfactant proteins A and D, may contribute to an individual's risk for infection (45)(46)(47). The recent findings by Lofgren et al (47) that the risk for severe respiratory syncytial virus infection has a genetic association related to specific surfactant protein A alleles point out the importance of variable host intrinsic immune responses at the genetic level.…”

Section: Il Concentrations From Tas Of Unexposed Controls Compared mentioning

confidence: 99%

Effects of Antenatal Colonization with Ureaplasma urealyticum on Pulmonary Disease in the Immature Baboon

et al. 2003

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Current nonhuman models for bronchopulmonary dysplasia have not included perinatal infection. We studied the effects of antenatal Ureaplasma urealyticum (Uu) infection in the 125-d immature baboon. Ten 125-d gestation (term ϭ 185 d) baboon dams were delivered after intra-amniotic inoculation with Uu. Serial blood and tracheal aspirate samples were analyzed for Uu colony-forming units, IL-6, IL-8, and cell counts. Physiologic parameters were serially recorded. Lung histology was examined after 14 d of ventilation and compared with unexposed controls. All Uu-exposed animals had Ͼ4 ϫ 10 2 CFU in tracheal aspirate at 24 h. Four of nine Uu animals remained heavily colonized [(ϩ) Uu] at necropsy (Ͼ6 ϫ 10 3 ). Five animals had negative or low tracheal colony-forming units. All Uu animals had significant increases for white blood cells, IL-6, and IL-8 in amniotic and fetal lung fluid. Compared with controls, (ϩ) Uu animals had significantly higher fraction of inspired oxygen, airway pressures, oxygenation index, and ventilation efficiency index between 48 and 240 h and had significantly elevated tracheal IL-6 and IL-8 concentrations between 72 and 240 h. Compared with controls (Ϫ) Uu animals had significantly better oxygenation index and ventilation efficiency index scores between 48 and 144 h. Lung histopathology in both Uu groups showed more severe bronchiolitis and interstitial pneumonitis compared with controls. Two patterns of disease were observed after Uu perinatal infection. Persistent colonization manifested a picture consistent with acute pneumonitis, worse lung function from 2 to 10 d, and prolonged elevated tracheal cytokines. Colonized animals that subsequently cleared Uu from the lung demonstrated early improved lung function compared with unexposed controls yet still manifested mixed bronchiolitis and interstitial pneumonitis at necropsy. Inherent immune system responses may determine outcome of perinatal Ureaplasma colonization. The pathogenesis of bronchopulmonary dysplasia (BPD) is incompletely understood, but pulmonary inflammation seems to play a critical key role (1-3). Pulmonary inflammation may be initiated by various insults, including hyperoxia, volutrauma, and infection. Recent reports suggest an important role for both postnatal and perinatal infection in the pathogenesis of BPD (4 -7).Evidence for microbial invasion of the amniotic cavity has been found in up to 80% of preterm births (8 ABSTRACT 797(Uu)(9 -11). The presence of Uu in the preterm respiratory tract has been correlated with elevated cellular and molecular markers of inflammation and associated with an increased risk for BPD (7,(12)(13)(14). Current nonhuman models for BPD are limited by the lack of perinatal infection as a confounding factor. A previous pilot study from this center demonstrated worse clinical and histologic hyaline membrane disease after Uu colonization of the 140-d preterm baboon (15). However, Ureaplasma colonization was conferred postnatally, and all animals were exposed to hyperoxia [fraction of inspired oxy...

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Section: Il Concentrations From Tas Of Unexposed Controls Compared mentioning

confidence: 99%

Effects of Antenatal Colonization with Ureaplasma urealyticum on Pulmonary Disease in the Immature Baboon

et al. 2003

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“…Hyperoxia may serve as a cofactor for Ureaplasma pulmonary dissemination similar to Pseudomonas (26) or cause persistence of Ureaplasma in the lung (27). In either case, the combination of hyperoxia and Ureaplasma appears to potentiate the pulmonary cellular inflammatory response (27) and/or proinflammatory cytokine response (28,29). Azithromycin treatment may limit the dissemination (26) or persistence of Ureaplasma in the lung or directly suppress the inflammatory response to hyperoxia (30) or Ureaplasma, or both.…”

Section: Discussionmentioning

confidence: 99%

“…One-day-old pups received either intraperitoneal erythromycin 20 mg/kg/dose twice a day for 3 d or azithromycin 12 mg/kg/dose daily for 3 d. Blood was collected by cardiac puncture at 1,5,7,23,25,29,31,47,49,53,55,72, and 96 h. Blood from two to three pups was pooled per data point, and two data points were obtained for each time point.…”

Section: Organismmentioning

confidence: 99%

Antibiotic Prophylaxis Improves Ureaplasma-Associated Lung Disease in Suckling Mice

et al. 2009

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Ureaplasma infection is associated with increased lung disease in high-risk neonates. Our goal was to determine the impact of antibiotic prophylaxis on Ureaplasma and oxygen-induced lung disease in newborn mice. In animal model development and prophylaxis experiments, pups were randomly assigned to either 0.8 or 0.21 inspired oxygen concentration [fraction of inspired oxygen (FiO 2 )] from 1 to 14 d of age and either Ureaplasma or 10 B media daily from 1 to 3 d. All pups were observed for growth and survival. Surviving pups had culture and PCR evaluated for blood, bronchoalveolar lavage, and lung, and lung weights, pathology, morphometry, histology, and immunohistochemistry were determined. In prophylaxis experiments, erythromycin, azithromycin, or normal saline was given for the first 3 d, and minimum inhibitory concentration and pharmacokinetics were determined. In model development, 0.8 FiO 2 and Ureaplasma infection survival and growth were significantly decreased and lung edema and inflammation were significantly increased. In prophylaxis experiments, we observed significantly improved survival and growth with azithromycin versus normal saline controls, whereas erythromycin was not significantly different from controls, and decreased inflammatory response with azithromycin versus normal saline and erythromycin. In a neonatal mouse model of Ureaplasma and oxygen-induced lung disease, appropriate antibiotic prophylaxis improves survival and morbidity and decreases lung inflammation. (Pediatr Res 66: 197-202, 2009)

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“…Surfactant, like meconium, is a very complex mixture of components and the anti-inflammatory properties of exogenous lung surfactant must also be considered (25). All animals received exogenous surfactant after meconium instillation, since this treatment is now considered routine.…”

Section: Discussionmentioning

confidence: 99%

CC10 Reduces Inflammation in Meconium Aspiration Syndrome in Newborn Piglets

Angert

Pilon²,

Chester

et al. 2007

Pediatr Res

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ABSTRACT:Complications from meconium aspiration syndrome (MAS) remain significant despite a variety of therapeutic interventions. Clara cell protein (CC10) is a novel anti-inflammatory agent that can also inhibit phospholipase A 2 (PLA 2 ) (an important component of meconium). The present study examined whether administration of recombinant human CC10 (rhCC10) would reduce inflammation and improve lung function in a piglet model of MAS. Following meconium instillation, piglets exhibited significant physiologic dysfunction that improved significantly after surfactant administration. Analysis of tracheal aspirates revealed significant increases in both tumor necrosis factor (TNF) ␣ and interleukin (IL)-8 after meconium instillation. rhCC10-treated animals had significantly lower TNF-␣ levels at 24 h (561 Ϯ 321 versus 1357 Ϯ 675 pg/mL, p Ͻ 0.05) compared with saline controls. There were no differences between rhCC10-treated and untreated groups with respect to other measured physiologic variables or inflammatory markers, including secretory PLA 2 activity. Histologic analyses revealed marked inflammatory infiltrates and thickened alveolar walls, but no significant differences among rhCC10 and control animals. Newborn piglets with MAS have significant physiologic dysfunction, marked inflammatory changes and histologic abnormalities, which was partially counteracted by a single dose of exogenous surfactant and rhCC10.

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Exogenous Bovine Surfactant Suppresses Tumor Necrosis Factor‐α Release by Murine Macrophages Stimulated by Genital Mycoplasmas

Cited by 12 publications

References 14 publications

Effects of Antenatal Colonization with Ureaplasma urealyticum on Pulmonary Disease in the Immature Baboon

Effects of Antenatal Colonization with Ureaplasma urealyticum on Pulmonary Disease in the Immature Baboon

Antibiotic Prophylaxis Improves Ureaplasma-Associated Lung Disease in Suckling Mice

CC10 Reduces Inflammation in Meconium Aspiration Syndrome in Newborn Piglets

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