The pattern of inflammation in rat sepsis due to enterotoxin - producing Staphylococcus aureus

A comparison with ischemia-reperfusion injury

Robert Y. Lin, Dhanonjoy C. Saha, Catherine J. Bernstein, Mark E. Astiz, Eric C. Rackow

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Sepsis and trauma have similarities in their immunopathologic profiles. Both conditions can result in multi-system organ failure which is sometimes associated with cytokine generation and inflammatory cell activation. Furthermore, decreases in peripheral blood monocyte expression of HLA-DR have been noted in both human sepsis and trauma. However, the magnitude, onset, and time course of such stimuli are often difficult to ascertain in human studies. Thus, to study a more detailed in vivo immunologic profile in these conditions, rat models were employed. Our aim was to describe and analyze cytokine and peripheral blood immunophenotype patterns in bacterially induced rat sepsis and to compare this to rat ischemia-reperfusion injury. Sprague- Dawley rats underwent either bacterial injection with enterotoxin producing Staphylococcus aureus or hind limb ischemia/reperfusion. Two bacterial doses which were either lethal or sublethal at 24-48 hours were utilized. Peripheral blood neutrophils and B-lymphocytes were studied for expression of β-integrins (CD11b and CD11b/c) and I-A, respectively, using flow cytometry. Corresponding plasma levels of TNF α and interferon γ were measured by ELISA. At 24 hr, a lethal bacterial dose injection resulted in significantly higher levels of neutrophil CD11b/c expression (p <0.005) compared with ischemia-reperfusion treatment. B-cell I-A expression was also higher in lethal sepsis. Gamma interferon levels were significantly higher in lethal sepsis compared with ischemia-reperfusion (p = 0.005). Studies over time showed that CD11b expression and interferon γ were both more marked at 6 hr than at 24 hr in lethal sepsis. This pattern was not observed in sublethal sepsis or in ischemia-reperfusion. CD11b/c expression on the other hand remained elevated at comparable levels at 6 and 24 hr in lethal sepsis. B- cell I-A expression in ischemia-reperfusion and sublethal sepsis decreased at 24 hr compared with baseline. Lethal sepsis in rats injected with enterotoxin producing staphylococcus results in phasic alterations in neutrophil CD11b and plasma interferon levels prior to death. In analogy to the findings of monocyte decreases in DR expression observed in human trauma and sepsis, rat B-cell I-A expression showed decreases in sublethal sepsis as well as in ischemia-reperfusion injury. However, this was not observed in lethal sepsis. These findings have implications in understanding the immunologic/inflammatory changes observed in human sepsis and trauma.

Original languageEnglish (US)
Pages (from-to)303-317
Number of pages15
JournalJournal of Medicine
Volume27
Issue number5-6
StatePublished - 1996
Externally publishedYes

Fingerprint

Enterotoxins
Reperfusion Injury
Staphylococcus aureus
Sepsis
Inflammation
Reperfusion
Ischemia
B-Lymphocytes
Interferons
Neutrophils
Wounds and Injuries
Monocytes
Cytokines
Injections
HLA-DR Antigens
Staphylococcus
Integrins
Interferon-gamma
Sprague Dawley Rats
Flow Cytometry

Keywords

  • CD11b
  • CD11b/c
  • I-A
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Medicine(all)

Cite this

The pattern of inflammation in rat sepsis due to enterotoxin - producing Staphylococcus aureus : A comparison with ischemia-reperfusion injury. / Lin, Robert Y.; Saha, Dhanonjoy C.; Bernstein, Catherine J.; Astiz, Mark E.; Rackow, Eric C.

In: Journal of Medicine, Vol. 27, No. 5-6, 1996, p. 303-317.

Research output: Contribution to journalArticle

Lin, Robert Y. ; Saha, Dhanonjoy C. ; Bernstein, Catherine J. ; Astiz, Mark E. ; Rackow, Eric C. / The pattern of inflammation in rat sepsis due to enterotoxin - producing Staphylococcus aureus : A comparison with ischemia-reperfusion injury. In: Journal of Medicine. 1996 ; Vol. 27, No. 5-6. pp. 303-317.
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