title: The pattern of inflammation in rat sepsis due to enterotoxin-producing Staphylococcus aureus: a comparison with ischemia-reperfusion injury.
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 beta-integrins (CD11b and CD11b/c) and I-A, respectively, using flow cytometry. Corresponding plasma levels of TNF alpha and interferon gamma were measured by ELISA. At 24 hr, a lethal bacterial 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 gamma 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.
authors.affiliation: Department of Medicine, Saint Vincents Hospital and Medical Center of New York, NY 10011, USA.
authors.forename: R Y
authors.initials: RY
authors.lastname: Lin
authors.forename: D C
authors.initials: DC
authors.lastname: Saha
authors.forename: C J
authors.initials: CJ
authors.lastname: Bernstein
authors.forename: M E
authors.initials: ME
authors.lastname: Astiz
authors.forename: E C
authors.initials: EC
authors.lastname: Rackow
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D016470:Bacteremia / Q000209:etiology* / Q000276:immunology; D018845:CD11 Antigens / Q000097:blood; D016207:Cytokines / Q000097:blood; D004768:Enterotoxins / Q000633:toxicity; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology* / Q000276:immunology; D013203:Staphylococcal Infections / Q000209:etiology* / Q000276:immunology; D013211:Staphylococcus aureus / Q000472:pathogenicity*
chemical_list: D018845:CD11 Antigens; D016207:Cytokines; D004768:Enterotoxins