Neutrophil-endothelium interactions in patients with systemic inflammatory response syndrome

Multiple Organ Dysfunction Syndrome (MODS) is associated with high mortality in patients admitted to the surgical intensive care unit (SICU). MODS begins with a systemic response described as Systemic Inflammatory Response Syndrome (SIRS). Studies on SIRS patients may provide an insight into the mechanisms by which SIRS progresses to MODS. In this thesis, the interactions between circulating polymorphonuclear neutrophils (PMNs) from patients with SIRS and endothelial cells (ECs) from human umbilical veins were measured in order to elucidate the mechanism for PMN adhesion and subsequent cytotoxicity of the ECs. PMNs from patients with SIRS were compared to PMNs from pre-operative surgical patients without SIRS and with healthy control subjects, in vitro. The results showed that PMNs adherence to ECs increased progressively from healthy controls to patients with SIRS. PMN-HUVE cytotoxicity, however, did not show this trend. PMNs from SIRS patients treated with lipopolysaccharide, unlike PMNs from patients without SIRS or healthy controls, showed no increase in PMN-EC adhesion. The results also showed that EC activation with TNF-$ alpha$ and Il-1$ beta$ led to high levels of PMN-EC adhesion and cytotoxicity, whereas PMN treatment with lipopolysaccharide played a lesser role. Autologous plasma provided significant protection from PMN mediated EC damage. From this data I conclude that activation of the EC by cytokines associated with SIRS is far more important in promoting PMN-EC adhesion and subsequent cytotoxicity than PMN stimulation with lipopolysaccharide and that there are host factors in plasma that modulate this response