Proteolytic activity and fatal gram-negative sepsis in burned mice

Effect of exogenous proteinase inhibition

A. N. Neely, R. G. Miller, I. A. Holder

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Circulating proteolytic activity (PA) increases following burn or surgical trauma. Challenging traumatized mice with the yeast Candida albicans further increases PA. Once a PA threshold has been passed, mortality increases as PA increases. The purposes of this study were to determine (i) if gram-negative bacterial challenge affects circulating PA and mortality as Candida challenge does and (ii) if proteinase inhibitor treatment with aprotinin, antithrombin III, and α 1-proteinase inhibitor decreases circulating PA and increases the survival of burned mice infected with a bacterium. For all bacteria tested (Proteus mirabilis, Pseudomonas aeruginosa, and Klebsiella pneumoniae), burn plus challenge significantly elevated PA and mortality above levels in mice that were only burned or only challenged. Quantitative culture counts indicated that the mice died of sepsis. Proteinase inhibitor treatment of mice burned and challenged with K. pneumoniae significantly decreased circulating PA, decreased the hepatic microbial load, and increased survival. Hence, in traumatized mice challenged with either C. albicans or gram- negative bacteria, a relationship exists between proteolytic load and subsequent septic death. Parallels between these animal studies and human studies are discussed.

Original languageEnglish (US)
Pages (from-to)2158-2164
Number of pages7
JournalInfection and Immunity
Volume62
Issue number6
StatePublished - 1994

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Sepsis
Peptide Hydrolases
Klebsiella pneumoniae
Candida albicans
Mortality
Bacteria
Proteus mirabilis
Aprotinin
Survival
Antithrombin III
Gram-Negative Bacteria
Candida
Pseudomonas aeruginosa
Yeasts
Liver
Wounds and Injuries

ASJC Scopus subject areas

  • Immunology

Cite this

Proteolytic activity and fatal gram-negative sepsis in burned mice : Effect of exogenous proteinase inhibition. / Neely, A. N.; Miller, R. G.; Holder, I. A.

In: Infection and Immunity, Vol. 62, No. 6, 1994, p. 2158-2164.

Research output: Contribution to journalArticle

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