Ureaplasma urealyticum respiratory tract colonization is associated with an increase in interleukin 1-beta and tumor necrosis factor alpha relative to interleukin 6 in tracheal aspirates of preterm infants

Patterson, Angela; Taciak, Vicki L; Lovchik, Judith C.; Fox, Renee E.; Campbell, Andrew B.; Viscardi, Rose M.

doi:10.1097/00006454-199804000-00011

Cited by 87 publications

(60 citation statements)

References 47 publications

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“…Similarly, several authors have reported an increase in proinflammatory cytokines in infants who are colonized with U. urealyticum (23,24). Our study adds further to this literature by suggesting that in infants who do not have clinical or laboratory evidence of sepsis, U. urealyticum must be considered as an important contributor to acute lung injury, as was demonstrated by an increase of pro-inflammatory cytokines, particularly IL-6 and IL-8, which were both increased at birth in these infants.…”

Section: Discussionmentioning

confidence: 85%

Pulmonary Ureaplasma urealyticum Is Associated with the Development of Acute Lung Inflammation and Chronic Lung Disease in Preterm Infants

et al. 2004

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Previously, we have reported marked pulmonary inflammation in infants who develop chronic lung disease of prematurity. We revisited these infants who did not have clinical or laboratory evidence of infection and searched for Ureaplasma urealyticum, group B streptococci, and other microbes by reverse transcription-PCR performed on RNA extracted from 93 bronchoalveolar lavage samples. From infants ventilated for respiratory distress syndrome, 6 (gestation, 28 wk; birthweight, 880 g) were positive for U. urealyticum and 11 (25 wk, 800 g) were negative. Five (83%) positive and four (36%) negative infants developed chronic lung disease. Each infant was colonized with either biovar 1 or biovar 2 but not both. U. urealyticum was very weakly detectable in two infants on d 1 but was detected in five of six infants at d 10. Furthermore, pulmonary neutrophils, alveolar macrophages, soluble intercellular adhesion molecule-1, and IL-1␤ on d 10 and IL-6 and IL-8 at d 1 were significantly increased in the positive group. A variety of organisms were identified in six samples between 14 and 21 d of age, but all samples were negative for group B streptococci. Our data suggest that U. urealyticum colonization is associated with the development of pulmonary inflammation in infants who subsequently develop chronic lung disease. CLD remains a common respiratory disorder of preterm infants. Despite significant advances with therapeutic modalities, including the introduction of surfactant, various modes of mechanical ventilation and regular use of antenatal corticosteroids, morbidity and mortality remain high. Many risk factors have been identified and these include mechanical ventilation, oxygen therapy, patent ductus arteriosus, and nosocomial infection. An area that has recently received much attention is antenatal infection (1, 2). Even before the infant is delivered, an inflammatory response has been noted and this inflammation appears to be associated with the development of respiratory disease in the newborn infant (3, 4). One candidate for initiating this inflammation is the mycoplasma Ureaplasma urealyticum (5, 6). This organism has been isolated from the lungs of infants who have developed CLD, but whether U. urealyticum causes acute lung injury in preterm infants or whether the association is with the degree of prematurity remains controversial (7). One approach to confirming or refuting this association is to study the link between the pulmonary inflammatory response, which has now been regularly reported in infants who develop CLD (8 -11), and the presence of U. urealyticum in the lungs of infants who develop CLD.Our previous data have demonstrated that proinflammatory cytokines IL-1 and IL-6, the potent neutrophil chemoattractant IL-8, and soluble adhesion molecule ICAM-1, as well as inflammatory cells, namely neutrophils, are increased in the lungs of infants who subsequently develop CLD (8, 9). These findings have been confirmed by many others (10, 11), and it is now generally accepted that pulmonary inflammation is a r...

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Section: Discussionmentioning

confidence: 85%

Pulmonary Ureaplasma urealyticum Is Associated with the Development of Acute Lung Inflammation and Chronic Lung Disease in Preterm Infants

et al. 2004

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“…Patterson et al 41 found significantly higher levels of interleukin-1␤ and tumor necrosis factor-␣ and significantly lower levels of interleukin-6 among infants colonized with U urealyticum on days 1 and 7 in comparison to noncolonized infants. Infants who ultimately developed CLD had significantly higher interleukin-1␤ and interleukin-1␤: interleukin-6 ratios.…”

Section: Discussionmentioning

confidence: 99%

Patterns of Colonization WithUreaplasma urealyticumDuring Neonatal Intensive Care Unit Hospitalizations of Very Low Birth Weight Infants and the Development of Chronic Lung Disease

et al. 2002

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ABSTRACT. Background. Ureaplasma urealyticum and its association with chronic lung disease (CLD) of prematurity has remained a controversial topic. To readdress this question, we performed a longitudinal study using culture and polymerase chain reaction to detect U urealyticum in the respiratory tract of very low birthweight infants throughout their neonatal intensive care unit hospitalizations.Methods. We screened 125 infants weighing <1500 g and/or <32 weeks' gestational age over a 12-month period, collecting endotracheal, nasopharyngeal, and throat specimens on days of age 1, 3, 7, and weekly thereafter. CLD was defined as dependency on supplemental oxygen at 28 days and at 36 weeks' postconceptional age.Results. Forty infants (32%) had 1 or more positive specimens by culture or polymerase chain reaction. We identified 3 patterns of U urealyticum colonization: persistently positive (n ‫؍‬ 18), early transient (n ‫؍‬ 14), and late acquisition (n ‫؍‬ 8). We compared the rates of CLD in each of the 3 colonized groups with the rate of CLD in the noncolonized group. We found a significantly higher rate of CLD at 28 days of age (odds ratio: 8.7; 95% confidence interval: 3.3, 23) and at 36 weeks' postconception (odds ratio: 38.5, 95% confidence interval: 4.0, 374) only for infants with persistently positive colonization.Conclusions. This study demonstrates that the risk of developing CLD varies with the pattern of U urealyticum colonization. Only the persistently positive colonization pattern, which accounted for 45% of the U urealyticumpositive infants, was associated with a significantly increased risk of development of CLD. Pediatrics 2002; 110(4). URL: http://www.pediatrics.org/cgi/content/full/ 110/4/e45; bronchopulmonary dysplasia, chronic lung disease, premature infant, polymerase chain reaction, Ureaplasma urealyticum, very low birth weight infant.

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“…[1][2][3][4][5][6][7][8] Since inflammation is a fundamental pathologic feature of CLD, the genetic variants of cytokine genes may be good candidates to explain some of the individual variation in the development of this complication. TNF-a is a central mediator in the inflammatory cascade and TA concentrations are elevated in infants who develop CLD.…”

Section: Discussionmentioning

confidence: 99%

“…Increased concentrations of inflammatory mediators in airway secretions during the first week of life have been associated with the development of CLD in the preterm infant suggesting that inflammation plays a central role in this condition. [1][2][3][4][5][6][7][8] Concentrations of tumor necrosis factor-a (TNF-a), a central mediator in the inflammatory cascade, are elevated during the first week of life in the tracheal aspirates (TA) obtained from infants who subsequently develop CLD. 1,2 The magnitude of TNF-a production may be in part genetically determined.…”

Section: Introductionmentioning

confidence: 99%

The TNF−α –308, MCP−1 –2518 and TGF−β1 +915 polymorphisms are not associated with the development of chronic lung disease in very low birth weight infants

et al. 2003

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Chronic lung disease (CLD) in premature newborns is associated with increased concentrations of inflammatory cytokines in tracheal aspirates (TA). We determined if polymorphisms of cytokine genes influence the risk of developing CLD by genotyping 178 mechanically ventilated very low birth weight (VLBW) infants for the tumor necrosis factor-a (TNF-a) À308 G/A, transforming growth factor-b 1 (TGF-b 1 ) +915 G/C and monocyte chemoattractant protein-1 (MCP-1) À2518 A/G polymorphisms. Genomic DNA was isolated from TA and genotypes determined by restriction length polymorphism. There was no effect of any of these polymorphisms on the development of CLD (29 vs 23%, P ¼ 0.371, TNF-a À308 AA/AG vs TNF-a À308 GG; 23 vs 26%, P ¼ 0.681, MCP-1 À2518 GG/AG vs MCP-1 À215-8 AA; 24 vs 24%, P ¼ 0.978, TGF-b 1 +915 CG vs TGF-b 1 +915 GG). TA IL-8 and MCP-1 concentrations were not different between genotype groups. Infants with the TNF-a À308 A allele had increased risk of IVH (RR 2.07; 95% CI 1.02-4.18, P ¼ 0.041) and infants with the TGF-b 1 +915 C allele were at greater risk of death (32 vs 9%, P ¼ 0.016). These data suggest that these polymorphisms do not play a significant role in determining risk for CLD in preterm infants, but may play a role in other complications in the neonatal period.

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Ureaplasma urealyticum respiratory tract colonization is associated with an increase in interleukin 1-beta and tumor necrosis factor alpha relative to interleukin 6 in tracheal aspirates of preterm infants

Cited by 87 publications

References 47 publications

Pulmonary Ureaplasma urealyticum Is Associated with the Development of Acute Lung Inflammation and Chronic Lung Disease in Preterm Infants

Pulmonary Ureaplasma urealyticum Is Associated with the Development of Acute Lung Inflammation and Chronic Lung Disease in Preterm Infants

Patterns of Colonization WithUreaplasma urealyticumDuring Neonatal Intensive Care Unit Hospitalizations of Very Low Birth Weight Infants and the Development of Chronic Lung Disease

The TNF−α –308, MCP−1 –2518 and TGF−β1 +915 polymorphisms are not associated with the development of chronic lung disease in very low birth weight infants

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