Chantal Parent

Neutrophil and endothelial cell interactions in sepsis. The role of adhesion molecules.

Although adhesion molecules present on circulating neutrophils and endothelial cells are essential for normal host defense, generalized activation of these molecules has been implicated in the inflammatory tissue injury occurring during sepsis and septic shock. A review of both preclinical and clinical studies suggests, however, that although these molecules mediate tissue injury related to a variety of microbial and host inflammatory mediators, their predominant role during sepsis with infection is a protective one.

Granulocyte Colony Stimulating Factor as a Therapy for Pneumonia and Sepsis in the Nonneutropenic Host: Preclinical and Clinical Trials

Outcome associated with severe pneumonia, especially when it is complicated by sepsis and septic shock remains poor in the nonneutropenic host despite our best conventional therapies (30 to 50%) (1,2). New modes of therapy are needed. An alternative to blocking the intense inflammatory response of sepsis, an approach which has not shown convincing benefit in clinical trials thus far, is to administer agents to augment host defense and better control the underlying infection. One such agent is recombinant granulocyte colony stimulating factor (G-CSF), a potent stimulator of neutrophil number and function (3,4). Similar to antiinflammatory agents however, despite promising results in preclinical studies, G-CSF has not shown convincing benefit in early clinical trials in nonneutropenic patients presenting with pneumonia or sepsis (5,6). While disappointing, our evolving preclinical and clinical experience with G-CSF may provide insight into ways to increase the effectiveness of this therapeutic approach in the future.