Plasma concentrations of inflammatory cytokines rise rapidly during ECMO-related SIRS due to the release of preformed stores in the intestine

R. Britt McIlwain, Joseph G. Timpa, Ashish R. Kurundkar, David W. Holt, David R. Kelly, Yolanda E. Hartman, Mary Lauren Neel, Rajendra K. Karnatak, Robert Schelonka, G. M. Anantharamaiah, Cheryl R. Killingsworth, Akhil Maheshwari

Research output: Contribution to journalArticle

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Abstract

Extracorporeal membrane oxygenation (ECMO) is a life-saving support system used in neonates and young children with severe cardiorespiratory failure. Although ECMO has reduced mortality in these critically ill patients, almost all patients treated with ECMO develop a systemic inflammatory response syndrome (SIRS) characterized by a cytokine storm, leukocyte activation, and multisystem organ dysfunction. We used a neonatal porcine model of ECMO to investigate whether rising plasma concentrations of inflammatory cytokines during ECMO reflect de novo synthesis of these mediators in inflamed tissues, and therefore, can be used to assess the severity of ECMO-related SIRS. Previously healthy piglets (3-week-old) were subjected to venoarterial ECMO for up to 8 h. SIRS was assessed by histopathological analysis, measurement of neutrophil activation (flow cytometry), plasma cytokine concentrations (enzyme immunoassays), and tissue expression of inflammatory genes (PCR/western blots). Mast cell degranulation was investigated by measurement of plasma tryptase activity. Porcine neonatal ECMO was associated with systemic inflammatory changes similar to those seen in human neonates. Tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) concentrations rose rapidly during the first 2 h of ECMO, faster than the tissue expression of these cytokines. ECMO was associated with increased plasma mast cell tryptase activity, indicating that increased plasma concentrations of inflammatory cytokines during ECMO may result from mast cell degranulation and associated release of preformed cytokines stored in mast cells. TNF-α and IL-8 concentrations rose faster in plasma than in the peripheral tissues during ECMO, indicating that rising plasma levels of these cytokines immediately after the initiation of ECMO may not reflect increasing tissue synthesis of these cytokines. Mobilization of preformed cellular stores of inflammatory cytokines such as in mucosal mast cells may have an important pathophysiological role in ECMO-related SIRS.

Original languageEnglish (US)
Pages (from-to)128-139
Number of pages12
JournalLaboratory Investigation
Volume90
Issue number1
DOIs
StatePublished - Jan 2010

Fingerprint

Systemic Inflammatory Response Syndrome
Extracorporeal Membrane Oxygenation
Intestines
Cytokines
Mast Cells
Cell Degranulation
Tryptases
Interleukin-8
Swine
Life Support Systems
Tumor Necrosis Factor-alpha
Newborn Infant
Neutrophil Activation
Plasma Cells
Immunoenzyme Techniques
Critical Illness

Keywords

  • CRP
  • Cytokines
  • Intestine
  • Mast cells
  • Neonate
  • Venoarterial

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Molecular Biology

Cite this

McIlwain, R. B., Timpa, J. G., Kurundkar, A. R., Holt, D. W., Kelly, D. R., Hartman, Y. E., ... Maheshwari, A. (2010). Plasma concentrations of inflammatory cytokines rise rapidly during ECMO-related SIRS due to the release of preformed stores in the intestine. Laboratory Investigation, 90(1), 128-139. https://doi.org/10.1038/labinvest.2009.119

Plasma concentrations of inflammatory cytokines rise rapidly during ECMO-related SIRS due to the release of preformed stores in the intestine. / McIlwain, R. Britt; Timpa, Joseph G.; Kurundkar, Ashish R.; Holt, David W.; Kelly, David R.; Hartman, Yolanda E.; Neel, Mary Lauren; Karnatak, Rajendra K.; Schelonka, Robert; Anantharamaiah, G. M.; Killingsworth, Cheryl R.; Maheshwari, Akhil.

In: Laboratory Investigation, Vol. 90, No. 1, 01.2010, p. 128-139.

Research output: Contribution to journalArticle

McIlwain, RB, Timpa, JG, Kurundkar, AR, Holt, DW, Kelly, DR, Hartman, YE, Neel, ML, Karnatak, RK, Schelonka, R, Anantharamaiah, GM, Killingsworth, CR & Maheshwari, A 2010, 'Plasma concentrations of inflammatory cytokines rise rapidly during ECMO-related SIRS due to the release of preformed stores in the intestine', Laboratory Investigation, vol. 90, no. 1, pp. 128-139. https://doi.org/10.1038/labinvest.2009.119
McIlwain, R. Britt ; Timpa, Joseph G. ; Kurundkar, Ashish R. ; Holt, David W. ; Kelly, David R. ; Hartman, Yolanda E. ; Neel, Mary Lauren ; Karnatak, Rajendra K. ; Schelonka, Robert ; Anantharamaiah, G. M. ; Killingsworth, Cheryl R. ; Maheshwari, Akhil. / Plasma concentrations of inflammatory cytokines rise rapidly during ECMO-related SIRS due to the release of preformed stores in the intestine. In: Laboratory Investigation. 2010 ; Vol. 90, No. 1. pp. 128-139.
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