Serum Cytokine and Chemokine Profiles in Neonates With Meconium Aspiration Syndrome

Okazaki, Kaoru; Kondo, Masatoshi; Katô, Masahiko; Kakinuma, Ryota; Nishida, Akira; Noda, Masahiro; Taniguchi, Kiyosu; Kimura, Hirokazu

doi:10.1542/peds.2007-1697

Cited by 38 publications

(25 citation statements)

References 45 publications

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“…Thus, it is reasonable to suggest that the profuse local inflammatory reaction was the primary cause of the observed systemic inflammatory response with increased formation of sC5b-9, IL-1β, and IL-6. This is in agreement with observations in neonatal patients [20]. …”

Section: Discussionsupporting

confidence: 94%

Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome

et al. 2018

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Background: Meconium aspiration syndrome (MAS) is a severe lung condition affecting newborns and it can lead to a systemic inflammatory response. We previously documented complement activation and cytokine release in a piglet MAS model. Additionally, we showed ex vivo that meconium-induced inflammation was dependent on complement and Toll-like receptors. Objectives: To assess the efficacy of the combined inhibition of complement (C5) and CD14 on systemic inflammation induced in a forceful piglet MAS model. Methods: Thirty piglets were randomly allocated to a treatment group receiving the C5-inhibitor SOBI002 and anti-CD14 (n = 15) and a nontreated control group (n = 15). MAS was induced by intratracheal meconium instillation, and the piglets were observed for 5 h. Complement, cytokines, and myeloperoxidase (MPO) were measured by ELISA. Results: SOBI002 ablated C5 activity and the formation of the terminal complement complex in vivo. The combined inhibition attenuated the inflammasome cytokines IL-1β and IL-6 by 60 (p = 0.029) and 44% (p = 0.01), respectively, and also MPO activity in the bronchoalveolar fluid by 42% (p = 0.017). Ex vivo experiments in human blood revealed that the combined regimen attenuated meconium-induced MPO release by 64% (p = 0.008), but there was only a negligible effect with single inhibition, indicating a synergic cross-talk between the key molecules C5 and CD14. Conclusion: Combined inhibition of C5 and CD14 attenuates meconium-induced inflammation in vivo and this could become a future therapeutic regimen for MAS.

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Section: Discussionsupporting

confidence: 94%

Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome

et al. 2018

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“…Although meconium may contain small amounts of LPS, our in vitro study shows that meconium-induced formation of proinflammatory cytokines are mainly caused by endogenous substances in meconium and not by LPS [7]. Most proinflammatory mediators measured in cord blood were elevated in sera from neonates with meconium aspiration syndrome [24]. Meconium-induced formation of both TNF and IL- 6 was higher in the CHF5633 group, while meconium-induced formation of IL-1β was higher in the poractant alfa group.…”

Section: Discussionmentioning

confidence: 99%

Effects of Natural versus Synthetic Surfactant with SP-B and SP-C Analogs in a Porcine Model of Meconium Aspiration Syndrome

Salvesen¹,

Curstedt

Mollnes

et al. 2013

Neonatology

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Background: Meconium displaces surfactant from the alveolar surface and inhibits its function. The development of active synthetic surfactants is complicated, especially to synthesize the hydrophobic surfactant proteins SP-B and SP-C. A synthetic surfactant, CHF5633 containing SP-B and SP-C analogs, has been designed to act similarly to the natural surfactant poractant alfa. Objective: To test the resistance to meconium inactivation of CHF5633 compared to poractant alfa. Secondary outcome measurements were respiratory and inflammatory parameters. Methods: Twenty-six newborn pigs, bodyweight 1.4-2.0 kg were randomized to receive either poractant alfa or CHF5633. After anesthesia, surgery and final stabilization, meconium was instilled endotracheally followed by surfactant. Bronchial lavage fluid was obtained before intervention and every second hour. Respiratory parameters were registered and blood samples drawn before intervention and every hour. Results: Surfactant was inactivated in both groups 6 h after meconium instillation, but CHF5633 was more resistant than poractant alfa in terms of lipid peroxidation. Respiratory parameters were similar in both groups. Inflammatory and hemostatic parameters differed between groups, suggesting that the surfactants may play different roles in the meconium-induced inflammatory process. Due to the differential effects and complex pattern observed, the data do not indicate that one of the surfactants was superior with respect to inflammatory and hemostatic responses. Conclusion: This study indicates that CHF5633 is as efficient as poractant alfa in experimental meconium aspiration syndrome.

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“…Their results give reason to argue against the view that anything else than meconium could cause MAS. Recently, a significant increase in proinflammatory cytokines as well as in anti-inflammatory IL-10 was documented within 6 h in serum from human neonates suffering from MAS [22]. The theme of cytokine expression and apoptosis in MAS pathophysiology has recently been reviewed by several authors [5,6,7].…”

Section: Inflammation In Mas - Lessons Learned From Experimental Studiesmentioning

confidence: 99%

Meconium Aspiration Syndrome: Possible Pathophysiological Mechanisms and Future Potential Therapies

et al. 2015

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Does meconium cause meconium aspiration syndrome (MAS) or is meconium discharge only a marker of fetal hypoxia? This dispute has lasted for centuries, but since the 1960s, detrimental effects of meconium itself on the lungs have been demonstrated in animal experiments. In clinical MAS, persistent pulmonary hypertension of the newborn is the leading cause of death in MAS. Regarding the complex chemical composition of meconium, it is difficult to identify a single agent responsible for the pathophysiology. However, considering that meconium is stored in the intestines, partly unexposed to the immune system, aspirated meconium could be recognized as ‘danger', representing damaged self. The common denominator in the pathophysiology could therefore be activation of innate immunity. Thus, a bulk of evidence implies that meconium is a potent activator of inflammatory mediators, including cytokines, complement, prostaglandins and reactive oxygen species. We hypothesize that the two main recognition systems of innate immunity, the Toll-like receptors and the complement system, recognize meconium as ‘danger', which leads not only to lung dysfunction but also to a systemic inflammatory response. This might have therapeutic implications in the future.

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Serum Cytokine and Chemokine Profiles in Neonates With Meconium Aspiration Syndrome

Cited by 38 publications

References 45 publications

Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome

Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome

Effects of Natural versus Synthetic Surfactant with SP-B and SP-C Analogs in a Porcine Model of Meconium Aspiration Syndrome

Meconium Aspiration Syndrome: Possible Pathophysiological Mechanisms and Future Potential Therapies

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