Systemic inflammation associated with mechanical ventilation among extremely preterm infants

Abstract

Little evidence is available to document that mechanical ventilation is an antecedent of systemic inflammation in preterm humans. We obtained blood on postnatal day 14 from 726 infants born before the 28th week of gestation and measured the concentrations of 25 inflammation-related proteins. We created multivariable models to assess the relationship between duration of ventilation and protein concentrations in the top quartile. Compared to newborns ventilated for fewer than 7 days (N=247), those ventilated for 14 days (N=330) were more likely to have elevated blood concentrations of pro-inflammatory cytokines (IL-1β, TNF-α), chemokines (IL-8, MCP-1), an adhesion molecule (ICAM-1), and a matrix metalloprotease (MMP-9), and less likely to have elevated blood concentrations of two chemokines (RANTES, MIP-1β), a matrix metalloproteinase (MMP-1), and a growth factor (VEGF). Newborns ventilated for 7-13 days (N=149) had systemic inflammation that approximated the pattern of newborns ventilated for 14 days. These relationships were not confounded by chorioamnionitis or antenatal corticosteroid exposure, and were not altered appreciably among infants with and without bacteremia. These findings suggest that two weeks of ventilation are more likely than shorter durations of ventilation to be accompanied by high blood concentrations of pro-inflammatory proteins indicative of systemic inflammation, and by low concentrations of proteins that might protect from inflammation-mediated organ injury.

Interleukin-1β Transfer across the Blood–Brain Barrier in the Ovine Fetus

“…This finding suggests that conditions such as perinatal inflammation that result in increases in systemic pro-inflammatory cytokines could facilitate cytokines to cross the intact BBB and cause brain injury before birth even under nonischemic conditions. 6,20,22 Several aspects of our study deserve comment. We used recombinantly expressed, pure ovine IL-1β protein to study blood-to-brain transport in fetal sheep.…”

“…4,6 Conditions such as systemic inflammation in the fetus and neonate, sepsis, necrotizing enterocolitis, and mechanical ventilation in the neonate, which are associated with elevations in systemic pro-inflammatory cytokines, are also associated with later brain injury in premature infants. [20][21][22] In addition, we have recently shown that BBB dysfunction represents an important component of ischemicreperfusion related brain injury in the fetus, 12 and that the proinflammatory cytokine IL-1β contributes to this barrier dysfunction. 19 Nonetheless, although it has been suggested that systemic cytokines might gain access to the fetal brain by crossing the BBB, 4 there is a paucity of direct experimental evidence to support this concept and no quantitative data measuring BBB permeability with cytokines in the fetal or neonatal brain.…”

“…4 Although there is a plethora of clinical evidence in support of the contention that pro-inflammatory cytokines could penetrate the immature BBB, there is a paucity of experimental evidence to show that systemic cytokines actually can cross the fetal BBB. [20][21][22] In the current study, we used the translational preclinical fetal sheep model of ischemia and reperfusion 23 along with radiolabeled IL-1β to quantify the influx of this pro-inflammatory cytokine across the BBB in the fetus. The development of the sheep brain has similarities to the human fetal and premature brain with reference to completion of neurogenesis, white-matter development, and onset of cerebral sulcation.…”

Non-Invasive Ventilation and Surfactant Therapy

“…Recent studies have shown that even noninjurious mechanical ventilation using normal tidal volumes activates a proinflammatory transcriptional program in the uninjured lung, which can prime the lung for injury [13]. Invasive mechanical ventilation not only initiates a pulmonary inflammatory response, but also a systemic inflammatory response in preterm infants [14]. The preterm infant lung is more vulnerable during the transitional period soon after birth.…”

Airway Humidification Reduces the Inflammatory Response During Mechanical Ventilation

“…[3][4][5] Infants are particularly susceptible to mechanical ventilation-mediated tissue damage, especially in the context of systemic inflammatory responses. 6 Others have demonstrated that me-chanical ventilation can lead to changes in lung pressure and tension, resulting in inflammatory cytokine release, alveolar edema, physiologic alveolar damage, increased alveolar permeability, and alveolar collapse. 5 However, it has been demonstrated that sufficient airway humidification can reduce the incidence of ventilator-associated pneumonia, the inflammation of the nasal mucous membranes, and the incidence of postoperative pulmonary complications.…”