Bactericidal/permeability increasing protein attenuates the myocardial inflammation/dysfunction that occurs with burn complicated by subsequent infection

Jureta W. Horton, David L. Maass, D. Jean White, Joseph P. Minei

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Intubation and mechanical ventilation after burn contribute to pneumonia-related infection. Although postburn presence or absence of endotoxin has been described, inactivation of Toll-like receptor 4 signaling has been shown to improve postburn organ function, suggesting that LPS participates in burn-related susceptibility to infection. We hypothesized that bactericidal/permeability-increasing protein (rBPI) given postburn would attenuate myocardial inflammation/dysfunction associated with postburn septic challenge given 7 days postburn. Rats were given burn over 40% total body surface area, lactated Ringer 4 ml·kg-1·% burn -1; burns received either vehicle or rBPI, 1 mg·kg -1·h-1 for 48 h postburn. Postburn day 7, subgroups of burns and shams were given intratracheal Klebsiella pneumoniae, 4 × 106 CFU to produce burn complicated by sepsis; additional sham and burn subgroups received intratracheal vehicle to produce sham sepsis. Vehicle-treated groups: 1) sham burn + sham sepsis 2) sham burn + sepsis, 3) burn + sham sepsis, 4) burn + sepsis. rBPI-treated groups: 5) sham burn + sham sepsis, 6) sham burn + sepsis, 7) burn + sham sepsis, 8) burn + sepsis. Cardiomyocyte cytokine secretion and myocardial function were studied 24 h after septic challenge, postburn day 8. Pneumonia-related infection 8 days after vehicle-treated burn produced myocyte cytokine secretion (pg/ml), indicated by increased myocyte TNF-α, 549 ± 46; IL-1-β, 50 ± 8; IL-6, 286 ± 3 levels compared with levels in sham myocytes (TNF-α, 88 ± 11; IL-1β-, 7 ± 1; IL-6, 74 ± 10; P < 0.05). Contractile dysfunction was evident from lower left ventricular pressure ±dP/dt values in this group compared with sham. rBPI attenuated myocyte cytokine responses to septic challenge and improved contractile function, suggesting that burn-related mobilization of microbial-like products contribute to postburn susceptibility to infection.

Original languageEnglish (US)
Pages (from-to)948-958
Number of pages11
JournalJournal of applied physiology
Volume103
Issue number3
DOIs
StatePublished - Sep 1 2007

Keywords

  • IL-1-β
  • IL-6 cytokines
  • Intratracheal Klebsiella pneumoniae challenge
  • Left ventricular function
  • Primary cardiomyocytes
  • TNF-α

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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