Oxidative stress in sepsis. Possible production of free radicals through an erythrocyte-mediated positive feedback mechanism

Yanaihara Pinchemel Amorim de Oliveira, Lain Carlos Pontes-de-Carvalho, Ricardo David Couto, Alberto Augusto Noronha-Dutra

Sepsis is an illness with a high morbidity for which no effective treatment exists. Its treatment has a high cost because it usually requires an intensive care unit and expensive antibiotics. The present study focus in the production of reactive oxygen species (ROS) in the early stages of sepsis. This study aimed at investigating the production of ROS during the inflammatory response in patients with sepsis. ROS production and insoluble myeloperoxidase obtained from fresh whole blood were measured by photon counting chemiluminescence in the blood of 18 septic patients and 12 healthy individuals. Modified red blood cells were evaluated by staining of blood smears. The production of reactive oxygen species by macrophages and polymorphonuclear leukocytes put into contact with modified red blood cells were also assessed by photon counting chemiluminescence. The appearance of oxidatively modified erythrocytes, which is an evidence of oxidative stress, was supported by the detection of reactive oxygen species and insoluble myeloperoxidase in the whole blood of all septic patients. Peroxynitrite was the main reactive oxygen species found in the whole blood. Oxidatively modified erythrocytes activated phagocytic cells in vitro, leading to the considerable production of free radicals. It was found that sepsis led to a high oxidative stress and to extensive modification of erythrocytes. It is proposed that a positive feedback mechanism, involving the activation of circulating leukocytes by these modified erythrocytes would maintain the pro-oxidative state even after the disappearance of bacteria.