Inhibition of neutrophil adhesion and neutrophil function in sepsis

Abstract

The care of pediatric patients has improved survival. However, many of these surviving patients, such as premature infants and patients with cancer, are predisposed to develop sepsis. Sepsis is associated with high morbidity and mortality rates despite excellent supportive care. There is accumulating evidence that a poorly compartmentalized inflammatory response involving neutrophils predominantly contributes to circulatory derangements and multiorgan system failure, which frequently complicate sepsis. As the molecular mechanisms of neutrophil accumulation have been elucidated, therapies directed against neutrophil adhesion and neutrophil activation responses have been investigated in animal models of sepsis and, to a limited extent, in humans. Therapies inhibiting adhesion molecules on neutrophils or endothelial cells should limit sepsis-induced nonspecific neutrophil responses, but the results of such trials have been mixed. Interventions targeting neutrophil activation responses have been promising. More research is necessary to determine specific molecular interventions inhibiting poorly compartmentalized inflammatory responses while maximizing neutrophil functions in clearing invading microorganisms. Copyright © 2001 by W.B. Saunders Company