Neutrophil Function in Severe Sepsis

Abstract

Sepsis and septic shock continue to be a major cause of morbidity and mortality in critically ill patients. During the onset of sepsis, several inflammatory mediators, including cytokines, chemokines and nitric oxide are released systemically and mediate most of the pathophysiological events present in sepsis and septic shock, such as cardiovascular dysfunction and target-organ lesions. Polymorphonuclear leukocytes are critical effector cells during the inflammatory process and their migration to the infection focus is extremely important for the local control of bacterial growth and consequently for the prevention of bacterial dissemination. In experimental models and in human sepsis a profound failure of neutrophil migration to the infection focus is observed. It seems that the failure of neutrophil migration is dependent on toll-like receptor 4 (TLR4) and mediated by cytokines and chemokines, which induce the production of nitric oxide that inhibits neutrophil adhesion to venular endothelium and also the neutrophil chemotactic ability.

High Mortality Associated with Hyperglycemia, Neutrophilia, and Lymphopenia in Critically Ill Patients

“…Previous studies have revealed the presence of hyperglycemia, neutrophilia or lymphopenia in patients with sepsis (Alves-Filho et al 2006;Corstjens et al 2006;Giamarellos-Bourboulis 2010). However, the presence of these three alterations together in a same group of patients has not been reported yet.…”

“…We know that the function of these cells is essential in the innate immunological response to the tissue injury. Some studies have shown impaired functions of neutrophils during sepsis (Alves-Filho et al 2006Giamarellos-Bourboulis 2010). On the other hand, some changes in neutrophil functions have been described in healthy patients after oral administration of a glucose load (Mohanty et al 2000).…”

Effect of pentoxifylline on lung inflammation and gas exchange in a sepsis-induced acute lung injury model

“…Alternatively, PTX could afford protection by its effects on inflammatory cells. Studies evaluating the effects of PTX on adhesion molecule expression have shown decreased P-selectin expression after hemorrhagic shock and decreased proinflammatory cytokine-induced ICAM-1 expression in human pulmonary epithelial cells and polymorphonuclear leukocytes (11,17,37).…”

“…Animals develop progressive bacteremia, with the release of multiple cytokines and chemokines into plasma, hypermetabolism, fever/ hypothermia, and other clinical features similar to those found in humans with sepsis (11). The main property of the lungs, gas exchange, combined with their delicate anatomical architecture, render them vulnerable during sepsis.…”

“…Sepsis has been studied experimentally by infusion of lipopolysaccharide (LPS) and dead or live bacteria, and the cecal ligation and puncture (CLP) procedure in order to mimic features of the septic state in humans (11). Animals develop progressive bacteremia, with the release of multiple cytokines and chemokines into plasma, hypermetabolism, fever/ hypothermia, and other clinical features similar to those found in humans with sepsis (11).…”