THE PATTERN OF INFLAMMATION IN RAT SEPSIS DUE TO ENTEROTOXIN-PRODUCING STAPHYLOCOCCUS-AUREUS - A COMPARISON WITH ISCHEMIA-REPERFUSION INJURY

Sepsis and trauma have similarities in their immunopathologic profiles . Both conditions can result in multi-system organ failure which is so metimes associated with cytokine generation and inflammatory cell acti vation. Furthermore, decreases in peripheral blood monocyte expression of HLA-DR have been noted in both human sepsis and trauma. However, t he magnitude, onset, and time course of such stimuli are often difficu lt to ascertain in human studies. Thus, to study a more detailed in vi vo immunologic profile in these conditions, rat models were employed. Our aim was to describe and analyze cytokine and peripheral blood immu nophenotype 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 we re either lethal or sublethal at 24-48 hours were utilized. Peripheral blood neutrophils and B-lymphocytes were studied for expression of be ta-integrins (CD11b and CD11b/c) and I-A, respectively, using flow cyt ometry. Corresponding plasma levels of TNF alpha and interferon gamma were measured by ELISA. At 24 hr, a lethal bacterial dose injection re sulted 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 w ere significantly higher in lethal sepsis compared with ischemia-reper fusion (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 letha l sepsis. This pattern was not observed in sublethal sepsis or in isch emia-reperfusion. CD11b/c expression on the other hand remained elevat ed at comparable levels at 6 and 24 hr in lethal sepsis. B-cell I-A ex pression in ischemia-reperfusion and sublethal sepsis decreased at 24 hr compared with baseline. Lethal sepsis in rats injected with enterot oxin producing staphylococcus results in phasic alterations in neutrop hil CD11b and plasma interferon levels prior to death. In analogy to t he findings of monocyte decreases in DR expression observed in human t rauma and sepsis, rat B-cell I-A expression showed decreases in sublet hal sepsis as well as in ischemia-reperfusion injury. However, this wa s not observed in lethal sepsis. These findings have implications in u nderstanding the immunologic/inflammatory changes observed in human se psis and trauma.